immunologic cytotoxicity

Summary

Summary: The phenomenon of target cell destruction by immunologically active effector cells. It may be brought about directly by sensitized T-lymphocytes or by lymphoid or myeloid "killer" cells, or it may be mediated by cytotoxic antibody, cytotoxic factor released by lymphoid cells, or complement.

Top Publications

  1. ncbi Sensitive and viable identification of antigen-specific CD8+ T cells by a flow cytometric assay for degranulation
    Michael R Betts
    Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, 40 Convent Drive, Bethesda, MD 20892, USA
    J Immunol Methods 281:65-78. 2003
  2. ncbi The biology of human natural killer-cell subsets
    M A Cooper
    Dept of Veterinary Biosciences and Comprehensive Cancer Center, The Ohio State University, 458A Starling-Loving Hall, 320 West 10th Ave, Columbus, OH 43210, USA
    Trends Immunol 22:633-40. 2001
  3. ncbi Human natural killer cells: a unique innate immunoregulatory role for the CD56(bright) subset
    M A Cooper
    Department of Internal Medicine, Division of Hematology/Oncology, The Ohio State University, Columbus, OH, USA
    Blood 97:3146-51. 2001
  4. pmc Rae1 and H60 ligands of the NKG2D receptor stimulate tumour immunity
    A Diefenbach
    Department of Molecular and Cell Biology and Cancer Research Laboratory, University of California, Berkeley 94720, USA
    Nature 413:165-71. 2001
  5. ncbi Control of effector CD8+ T cell function by the transcription factor Eomesodermin
    Erika L Pearce
    Abramson Family Cancer Research Institute, and Department of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA
    Science 302:1041-3. 2003
  6. ncbi The immunological synapse of CTL contains a secretory domain and membrane bridges
    J C Stinchcombe
    Sir William Dunn School of Pathology, South Parks Road, Oxford, OX1 3RE, United Kingdom
    Immunity 15:751-61. 2001
  7. ncbi Activation of NK cells and T cells by NKG2D, a receptor for stress-inducible MICA
    S Bauer
    Fred Hutchinson Cancer Research Center, Clinical Research Division, 1100 Fairview Avenue North, Seattle, WA 98109, USA
    Science 285:727-9. 1999
  8. ncbi Multiple defects of immune cell function in mice with disrupted interferon-gamma genes
    D K Dalton
    Genentech Inc, South San Francisco, CA 94080
    Science 259:1739-42. 1993
  9. ncbi Activating receptors and coreceptors involved in human natural killer cell-mediated cytolysis
    A Moretta
    Dipartimento di Medicina Sperimentale, Universita degli Studi di Genova, Italy
    Annu Rev Immunol 19:197-223. 2001
  10. pmc Broad tumor-associated expression and recognition by tumor-derived gamma delta T cells of MICA and MICB
    V Groh
    Fred Hutchinson Cancer Research Center, Clinical Research Division, 1100 Fairview Avenue North, Seattle, WA 98109, USA
    Proc Natl Acad Sci U S A 96:6879-84. 1999

Research Grants

Detail Information

Publications289 found, 100 shown here

  1. ncbi Sensitive and viable identification of antigen-specific CD8+ T cells by a flow cytometric assay for degranulation
    Michael R Betts
    Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, 40 Convent Drive, Bethesda, MD 20892, USA
    J Immunol Methods 281:65-78. 2003
    ....
  2. ncbi The biology of human natural killer-cell subsets
    M A Cooper
    Dept of Veterinary Biosciences and Comprehensive Cancer Center, The Ohio State University, 458A Starling-Loving Hall, 320 West 10th Ave, Columbus, OH 43210, USA
    Trends Immunol 22:633-40. 2001
    ..In addition, we will discuss other cell-surface receptors expressed differentially by human NK-cell subsets and the distinct functional properties of these subsets...
  3. ncbi Human natural killer cells: a unique innate immunoregulatory role for the CD56(bright) subset
    M A Cooper
    Department of Internal Medicine, Division of Hematology/Oncology, The Ohio State University, Columbus, OH, USA
    Blood 97:3146-51. 2001
    ..It is proposed that human CD56(bright) NK cells have a unique functional role in the innate immune response as the primary source of NK cell-derived immunoregulatory cytokines, regulated in part by differential monokine production...
  4. pmc Rae1 and H60 ligands of the NKG2D receptor stimulate tumour immunity
    A Diefenbach
    Department of Molecular and Cell Biology and Cancer Research Laboratory, University of California, Berkeley 94720, USA
    Nature 413:165-71. 2001
    ....
  5. ncbi Control of effector CD8+ T cell function by the transcription factor Eomesodermin
    Erika L Pearce
    Abramson Family Cancer Research Institute, and Department of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA
    Science 302:1041-3. 2003
    ..We suggest that Eomesodermin is likely to complement the actions of T-bet and act as a key regulatory gene in the development of cell-mediated immunity...
  6. ncbi The immunological synapse of CTL contains a secretory domain and membrane bridges
    J C Stinchcombe
    Sir William Dunn School of Pathology, South Parks Road, Oxford, OX1 3RE, United Kingdom
    Immunity 15:751-61. 2001
    ..Electron microscopy reveals continuities forming membrane bridges between the CTL and target cell membranes, suggesting a possible mechanism for this transfer...
  7. ncbi Activation of NK cells and T cells by NKG2D, a receptor for stress-inducible MICA
    S Bauer
    Fred Hutchinson Cancer Research Center, Clinical Research Division, 1100 Fairview Avenue North, Seattle, WA 98109, USA
    Science 285:727-9. 1999
    ..These results define an activating immunoreceptor-MHC ligand interaction that may promote antitumor NK and T cell responses...
  8. ncbi Multiple defects of immune cell function in mice with disrupted interferon-gamma genes
    D K Dalton
    Genentech Inc, South San Francisco, CA 94080
    Science 259:1739-42. 1993
    ..Resting splenic natural killer cell activity was reduced in IFN-gamma-deficient mice. Thus, IFN-gamma is essential for the function of several cell types of the murine immune system...
  9. ncbi Activating receptors and coreceptors involved in human natural killer cell-mediated cytolysis
    A Moretta
    Dipartimento di Medicina Sperimentale, Universita degli Studi di Genova, Italy
    Annu Rev Immunol 19:197-223. 2001
    ..Indeed, in patients with the X-linked lymphoproliferative disease, the inability to control Epstein-Barr virus infections may be consequent to a major dysfunction of 2B4 that exerts inhibitory instead of activating functions...
  10. pmc Broad tumor-associated expression and recognition by tumor-derived gamma delta T cells of MICA and MICB
    V Groh
    Fred Hutchinson Cancer Research Center, Clinical Research Division, 1100 Fairview Avenue North, Seattle, WA 98109, USA
    Proc Natl Acad Sci U S A 96:6879-84. 1999
    ..These results raise the possibility that an induced expression of MICA/B, by conditions that may be related to tumor homeostasis and growth, could play a role in immune responses against tumors...
  11. ncbi Recognition of stress-induced MHC molecules by intestinal epithelial gammadelta T cells
    V Groh
    Fred Hutchinson Cancer Research Center, Clinical Research Division, 1100 Fairview Avenue North, Seattle, WA 98109, USA
    Science 279:1737-40. 1998
    ..Thus, these molecules may broadly regulate protective responses by the Vdelta1 gammadelta T cells in the epithelium of the intestinal tract...
  12. ncbi An activating immunoreceptor complex formed by NKG2D and DAP10
    J Wu
    DNAX Research Institute, 901 California Avenue, Palo Alto, CA 94304, USA
    Science 285:730-2. 1999
    ..Thus, NKG2D-DAP10 receptor complexes may activate NK and T cell responses against MICA-bearing tumors...
  13. pmc A common inhibitory receptor for major histocompatibility complex class I molecules on human lymphoid and myelomonocytic cells
    M Colonna
    Basel Institute for Immunology, Basel CH 4005, Switzerland
    J Exp Med 186:1809-18. 1997
    ..These results suggest that diverse leukocyte lineages have adopted recognition of self-MHC class I molecules as a common strategy to control cellular activation during an immune response...
  14. ncbi Recognition of viral hemagglutinins by NKp44 but not by NKp30
    T I Arnon
    The Lautenberg Center for General and Tumor Immunology, The Hebrew University-Hadassah Medical School, Jerusalem, Israel
    Eur J Immunol 31:2680-9. 2001
    ..221 cells expressing MHC class I proteinsresulted in the abrogation of the inhibition by NK clones expressing high levels of NKp44. In addition, the binding of NKp44 to HA improves the ability of some NK clones to lyse IV infected cells...
  15. ncbi Activated, but not resting, T cells can be recognized and killed by syngeneic NK cells
    Brian A Rabinovich
    Department of Medical Biophysics, Ontario Cancer Institute, Toronto, Canada
    J Immunol 170:3572-6. 2003
    ..Our data provide a basis for studying a role for NK cells in T cell regulation...
  16. ncbi CD107a as a functional marker for the identification of natural killer cell activity
    Galit Alter
    Partners AIDS Research Center, Massachusetts General Hospital and Division of AIDS, Harvard Medical School, Massachusetts, USA
    J Immunol Methods 294:15-22. 2004
    ..Cumulatively, the data presented here demonstrate that CD107a is a sensitive marker of NK cell activity...
  17. ncbi Lymphocyte-mediated cytotoxicity
    John H Russell
    Department of Molecular Biology and Pharmacology, Washington University School of Medicine, St Louis, Missouri 63110, USA
    Annu Rev Immunol 20:323-70. 2002
    ..host disease, but oversuppression of these pathways may also lead to increased viral susceptibility and/or decreased tumor cell killing...
  18. ncbi Recognition of haemagglutinins on virus-infected cells by NKp46 activates lysis by human NK cells
    O Mandelboim
    The Lautenberg Center for General and Tumor Immunology, The Hebrew University-Hadassha Medical School, Jerusalem, Israel
    Nature 409:1055-60. 2001
    ..These findings indicate how NKp46-expressing NK cells may recognize target cells infected by influenza or parainfluenza without the decreased expression of target-cell MHC class I protein...
  19. ncbi Regulation of cutaneous malignancy by gammadelta T cells
    M Girardi
    Department of Dermatology and Yale Skin Diseases Research Core Center, King s College, London SE1 9RT, UK
    Science 294:605-9. 2001
    ..Thus, local T cells may use evolutionarily conserved proteins to negatively regulate malignancy...
  20. ncbi An antimicrobial activity of cytolytic T cells mediated by granulysin
    S Stenger
    Department of Medicine, UCLA School of Medicine, Los Angeles, CA 90095, USA
    Science 282:121-5. 1998
    ..The ability of CTLs to kill intracellular M. tuberculosis was dependent on the presence of granulysin in cytotoxic granules, defining a mechanism by which T cells directly contribute to immunity against intracellular pathogens...
  21. ncbi Requirement for Stat4 in interleukin-12-mediated responses of natural killer and T cells
    W E Thierfelder
    Department of Biochemistry, St Jude Children s Research Hospital, Memphis, Tennessee 38105, USA
    Nature 382:171-4. 1996
    ..However, all IL-12 functions tested were disrupted, including the induction of IFN-gamma, mitogenesis, enhancement of natural killer cytolytic function and Th1 differentiation...
  22. pmc Cytolytic granule polarization and degranulation controlled by different receptors in resting NK cells
    Yenan T Bryceson
    Laboratory of Immunogenetics, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, MD 20852, USA
    J Exp Med 202:1001-12. 2005
    ..These data show that cytotoxicity by resting NK cells is controlled tightly by separate or cooperative signals from different receptors for granule polarization and degranulation...
  23. pmc Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) contributes to interferon gamma-dependent natural killer cell protection from tumor metastasis
    M J Smyth
    Cancer Immunology, Sir Donald and Lady Trescowthick Laboratories, Peter MacCallum Cancer Institute, East Melbourne, Victoria 3002, Australia
    J Exp Med 193:661-70. 2001
    ..These results indicated that TRAIL induction on NK cells plays a critical role in IFN-gamma-mediated antimetastatic effects of IL-12 and alpha-GalCer...
  24. ncbi CD4+ T cells are required for secondary expansion and memory in CD8+ T lymphocytes
    Edith M Janssen
    Division of Cellular Immunology and Division of Developmental Immunology, La Jolla Institute for Allergy and Immunology, 10355 Science Center Drive, San Diego, California 92121, USA
    Nature 421:852-6. 2003
    ..Our results demonstrate that T-cell help is 'programmed' into CD8+ T cells during priming, conferring on these cells a hallmark of immune response memory: the capacity for functional expansion on re-encounter with antigen...
  25. ncbi Distinct effects of T-bet in TH1 lineage commitment and IFN-gamma production in CD4 and CD8 T cells
    Susanne J Szabo
    Department of Immunology and Infectious Diseases, Harvard School of Public Health, Boston, MA 02115, USA
    Science 295:338-42. 2002
    ..This difference is also apparent in the function of these cell subsets. Thus, the regulation of a single cytokine, IFN-gamma, is controlled by distinct transcriptional mechanisms within the T cell lineage...
  26. ncbi Impaired IL-12 responses and enhanced development of Th2 cells in Stat4-deficient mice
    M H Kaplan
    Department of Cancer Biology, Harvard School of Public Health, Boston, Massachusetts 02115, USA
    Nature 382:174-7. 1996
    ..These results demonstrate that Stat4 is essential for mediating responses to IL-12 in lymphocytes, and regulating the differentiation of both Th1 and Th2 cells...
  27. pmc p46, a novel natural killer cell-specific surface molecule that mediates cell activation
    S Sivori
    Istituto di Istologia ed Embriologia Generale, Universita di Genova, Genova, Italy
    J Exp Med 186:1129-36. 1997
    ..Both the unique cellular distribution and functional capability of p46 molecules suggest a possible role in the mechanisms of non-major histocompatibility complex-restricted cytolysis mediated by human NK cells...
  28. ncbi Inhibition of the NKp30 activating receptor by pp65 of human cytomegalovirus
    Tal I Arnon
    The Lautenberg Center for General and Tumor Immunology, The Hebrew University Hadassah Medical School, Jerusalem 91120, Israel
    Nat Immunol 6:515-23. 2005
    ..Thus, pp65 is a ligand for the NKp30 receptor and demonstrates a unique mechanism by which an intracellular viral protein causes general suppression of natural killer cell cytotoxicity by specific interaction with an activating receptor...
  29. ncbi DNAM-1, a novel adhesion molecule involved in the cytolytic function of T lymphocytes
    A Shibuya
    DNAX Research Institute of Molecular and Cellular Biology, Department of Human Immunology, Palo Alto, California 94304 1104, USA
    Immunity 4:573-81. 1996
    ..In addition, DNAM-1 is a tyrosine-phosphorylated signal-transducing molecule that participates in primary adhesion during cytotoxic T lymphocyte (CTL)-mediated cytotoxicity...
  30. pmc Differential tumor surveillance by natural killer (NK) and NKT cells
    M J Smyth
    Cellular Cytotoxicity Laboratory, Austin Research Institute, Austin and Repatriation Medical Centre, Heidelberg, 3084 Victoria, Australia
    J Exp Med 191:661-8. 2000
    ..This is the first description of an antitumor function for NKT cells in the absence of exogenously administered potent stimulators such as IL-12 or alpha-galactosylceramide...
  31. ncbi Immune responses in interleukin-2-deficient mice
    T M Kundig
    Institute of Experimental Immunology, University of Zurich, Switzerland
    Science 262:1059-61. 1993
    ..Natural killer cell activity was markedly reduced but inducible. These normal in vivo immune responses in IL-2-deficient mice question the importance of IL-2 as defined by in vitro studies...
  32. pmc Contact-dependent stimulation and inhibition of dendritic cells by natural killer cells
    Diego Piccioli
    IRIS, Department of Immunology, Chiron S p A, 53100 Siena, Italy
    J Exp Med 195:335-41. 2002
    ..Resting NK cells also stimulated autologous DC maturation in a TNF-alpha/contact-dependent manner, however, increasing the NK/DC ratio only led to an enhancement of this effect...
  33. pmc NKp44, a novel triggering surface molecule specifically expressed by activated natural killer cells, is involved in non-major histocompatibility complex-restricted tumor cell lysis
    M Vitale
    Istituto Nazionale per la Ricerca sul Cancro and Centro Biotecnologie Avanzate, 16132 Genova, Italy
    J Exp Med 187:2065-72. 1998
    ....
  34. ncbi The role of the NKG2D immunoreceptor in immune cell activation and natural killing
    Amanda M Jamieson
    Department of Molecular and Cell Biology and Cancer Research Laboratory, 489 Life Sciences Addition, University of California, Berkeley, 94720, USA
    Immunity 17:19-29. 2002
    ..In contrast, NKG2D costimulates activated CD8(+) T cells. Thus, NKG2D engagement directly stimulates NK cells and macrophages, costimulates CD8(+) T cells, and plays a substantial role in natural killing...
  35. ncbi Coordinated and distinct roles for IFN-alpha beta, IL-12, and IL-15 regulation of NK cell responses to viral infection
    Khuong B Nguyen
    Deparment of Molecular Microbiology and Immunology, Brown University, Providence, RI 02912, USA
    J Immunol 169:4279-87. 2002
    ....
  36. pmc Identification and molecular characterization of NKp30, a novel triggering receptor involved in natural cytotoxicity mediated by human natural killer cells
    D Pende
    Istituto Nazionale per la Ricerca sul Cancro, 16132 Genova, Italy
    J Exp Med 190:1505-16. 1999
    ..Moreover, we show that NKp30 is encoded by the previously identified 1C7 gene, for which the function and the cellular distribution of the putative product were not identified in previous studies...
  37. ncbi Cutting edge: lectin-like transcript-1 is a ligand for the inhibitory human NKR-P1A receptor
    David B Rosen
    Department of Microbiology and Immunology, The Cancer Research Institute, and Biomedical Sciences Graduate Program, University of California, San Francisco, CA 94143, USA
    J Immunol 175:7796-9. 2005
    ..Moreover, LLT1 on target cells can inhibit NK cytotoxicity via interactions with NKR-P1A...
  38. ncbi Cutting edge: lectin-like transcript 1 is a ligand for the CD161 receptor
    Hatice Aldemir
    Institut de Pharmacologie Moleculaire et Cellulaire, Centre National de la Recherche Scientifique Université de Nice Sophia Antipolis Unité Mixte de Recherche 6097, Sophia Antipolis, France
    J Immunol 175:7791-5. 2005
    ..Conversely, LLT1/CD161 interaction in the presence of a TCR signal enhanced IFN-gamma production by T cells. These findings identify a novel ligand/receptor pair that differentially regulate NK and T cell functions...
  39. ncbi The Fas death factor
    S Nagata
    Osaka Bioscience Institute, Japan
    Science 267:1449-56. 1995
    ..Malfunction of the Fas system causes lymphoproliferative disorders and accelerates autoimmune diseases, whereas its exacerbation may cause tissue destruction...
  40. ncbi Cutting edge: CD96 (tactile) promotes NK cell-target cell adhesion by interacting with the poliovirus receptor (CD155)
    Anja Fuchs
    Department of Pathology and Immunology, Washington University School of Medicine, St Louis, MO 63110, USA
    J Immunol 172:3994-8. 2004
    ..As PVR is highly expressed in certain tumors, this receptor system may be critical for NK cell recognition of tumors...
  41. ncbi Cis association of Ly49A with MHC class I restricts natural killer cell inhibition
    Marie Agnès Doucey
    Institute of Biochemistry, University of Lausanne, Ch des Boveresses 155, 1066 Epalinges, Switzerland
    Nat Immunol 5:328-36. 2004
    ..By lowering the threshold at which NK cell activation exceeds NK cell inhibition, cis interaction allows optimal discrimination of normal and abnormal host cells...
  42. ncbi Centrosome polarization delivers secretory granules to the immunological synapse
    Jane C Stinchcombe
    Sir William Dunn School of Pathology, South Parks Road, Oxford OX1 3RE, UK
    Nature 443:462-5. 2006
    ..These data show that CTLs use a previously unreported mechanism for delivering secretory granules to the immunological synapse, with granule secretion controlled by centrosome delivery to the plasma membrane...
  43. pmc B7H costimulates clonal expansion of, and cognate destruction of tumor cells by, CD8(+) T lymphocytes in vivo
    X Liu
    Department of Pathology and Comprehensive Cancer Center, Ohio State University Medical Center, Columbus, OH 43210, USA
    J Exp Med 194:1339-48. 2001
    ..Taken together, our results reveal that B7H costimulates clonal expansion of, and cognate destruction by CD8(+) T lymphocytes in vivo...
  44. pmc Shared reactivity of V{delta}2(neg) {gamma}{delta} T cells against cytomegalovirus-infected cells and tumor intestinal epithelial cells
    Franck Halary
    UMR 5164, Centre National de la Recherche Scientifique, IFR 66, Universite Bordeaux 2, 33076 Bordeaux, France
    J Exp Med 201:1567-78. 2005
    ....
  45. ncbi Cytotoxicity mediated by T cells and natural killer cells is greatly impaired in perforin-deficient mice
    D Kagi
    Department of Pathology, University of Zurich, Switzerland
    Nature 369:31-7. 1994
    ..The mice fail to clear lymphocytic choriomeningitis virus and they eliminate fibrosarcoma tumour cells with reduced efficiency. Perforin is therefore a key effector molecule for T-cell- and natural killer-cell-mediated cytolysis...
  46. ncbi Natural killer cells and viral infections
    Anthony R French
    Howard Hughes Medical Institute, Rheumatology Division, Box 8045, Washington University Medical Center, 660 South Euclid Avenue, St Louis, MO 63110, USA
    Curr Opin Immunol 15:45-51. 2003
  47. ncbi Ly-6A is critical for the function of double negative regulatory T cells
    Zhu Xu Zhang
    Department of Laboratory Medicine and Pathobiology, University of Toronto, Multi Organ Transplantation Program, Toronto General Research Institute, University Health Network, Toronto, Canada
    Eur J Immunol 32:1584-92. 2002
    ..Taken together, our data indicate that Ly-6A plays a crucial role in DN T cell-mediated regulation in vitro and in vivo, perhaps by enhancing DN-CD8+ T cell signaling...
  48. ncbi Cutting edge: MHC class II-restricted killing in vivo during viral infection
    Evan R Jellison
    Department of Pathology, University of Massachusetts Medical School, Worcester, MA 01655, USA
    J Immunol 174:614-8. 2005
    ..In this study, we demonstrate CD4-dependent MHC class II-restricted killing in lymphocytic choriomeningitis virus-infected mice in vivo using an in vivo cytotoxicity assay that features class II-expressing B cells as targets...
  49. pmc NCRs and DNAM-1 mediate NK cell recognition and lysis of human and mouse melanoma cell lines in vitro and in vivo
    Tadepally Lakshmikanth
    Department of Experimental and Clinical Medicine, University of Catanzaro Magna Graecia, Italy
    J Clin Invest 119:1251-63. 2009
    ....
  50. ncbi Analysis of the receptor-ligand interactions in the natural killer-mediated lysis of freshly isolated myeloid or lymphoblastic leukemias: evidence for the involvement of the Poliovirus receptor (CD155) and Nectin-2 (CD112)
    Daniela Pende
    Istituto Nazionale per la Ricerca sul Cancro, L go R Benzi 10, 16132 Genova, Italy
    Blood 105:2066-73. 2005
    ..In most leukemias, both CD48 and NTBA were down-regulated. The correlation found between marker expression and susceptibility to lysis may reveal useful information for NK-based immunotherapy...
  51. ncbi CD4(+) and CD8(+) T cells kill intracellular Mycobacterium tuberculosis by a perforin and Fas/Fas ligand-independent mechanism
    D H Canaday
    Division of Infectious Diseases, Case Western Reserve University School of Medicine and University Hospitals of Cleveland, Cleveland, OH 44106, USA
    J Immunol 167:2734-42. 2001
    ..Thus, perforin and CD95-CD95L were not involved in CD4(+) and CD8(+) T cell mediated restriction of MTB growth...
  52. ncbi Impaired proliferative response of V alpha 24 NKT cells from cancer patients against alpha-galactosylceramide
    Kazuhiko Yanagisawa
    Department of Surgery, Institute of Clinical Medicine, University of Tsukuba, Tsukuba Science City, Ibaraki, Japan
    J Immunol 168:6494-9. 2002
    ..These results suggest that some functions of NKT cells in cancer patients are impaired, and this observation carries significant implications for immunotherapy-based cancer treatments...
  53. pmc Reciprocal activating interaction between natural killer cells and dendritic cells
    Franca Gerosa
    Department of Pathology, Section of Immunology, University of Verona, 37100 Verona, Italy
    J Exp Med 195:327-33. 2002
    ..These data demonstrated for the first time a bidirectional cross talk between NK cells and DC, in which NK cells activated by IL-2 or by mature DC induce DC maturation...
  54. pmc Concerted action of the FasL/Fas and perforin/granzyme A and B pathways is mandatory for the development of early viral hepatitis but not for recovery from viral infection
    S Balkow
    Max Planck Institut fur Immunbiologie, 79108 Freiburg, Universitat Freiburg, 79104 Freiburg, Germany
    J Virol 75:8781-91. 2001
    ....
  55. ncbi The functional profile of primary human antiviral CD8+ T cell effector activity is dictated by cognate peptide concentration
    Michael R Betts
    Immunology Laboratory, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA
    J Immunol 172:6407-17. 2004
    ..The inherent ability of viruses to induce high or low Ag states may be the primary determinant of the cytokine vs cytolytic nature of the virus-specific CD8(+) T cell response...
  56. ncbi IL-21 down-regulates NKG2D/DAP10 expression on human NK and CD8+ T cells
    Steven J Burgess
    Receptor Cell Biology Section, Laboratory of Allergic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, MD 20852, USA
    J Immunol 176:1490-7. 2006
    ..These data indicate that IL-21 is able to channel NK and CD8+ T cell function by altering the expression pattern of activation/costimulatory receptors...
  57. ncbi NK cells and the tumour microenvironment: implications for NK-cell function and anti-tumour activity
    Per A Albertsson
    Department of Oncology, Sahlgrenska University Hospital, S 41345, Goteborg, Sweden
    Trends Immunol 24:603-9. 2003
    ..New insights into the migration of NK cells, their activation status and production of matrix-degrading proteases might help to overcome this localization defect, with implications for the treatment of human cancer...
  58. ncbi Dendritic cells loaded with killed allogeneic melanoma cells can induce objective clinical responses and MART-1 specific CD8+ T-cell immunity
    Anna K Palucka
    Baylor Institute for Immunology Research, Sammons Cancer Center, 3434 Live Oak, Dallas, TX 75204, USA
    J Immunother 29:545-57. 2006
    ..Thus, the present results justify the design of larger follow-up studies to assess the clinical response to DC vaccines loaded with killed allogeneic tumor cells in patients with metastatic melanoma...
  59. ncbi Granzyme A induces caspase-independent mitochondrial damage, a required first step for apoptosis
    Denis Martinvalet
    The CBR Institute for Biomedical Research and Department of Pediatrics, Harvard Medical School, Boston, MA 02115, USA
    Immunity 22:355-70. 2005
    ..Superoxide scavengers also block apoptosis by CTLs expressing GzmA and/or GzmB. Therefore, mitochondrial damage is an essential first step in killer cell granule-mediated pathways of apoptosis...
  60. ncbi Enhancement of CD8+ T cell responses by ICOS/B7h costimulation
    J J Wallin
    Immunology Division, Cancer Research Laboratory, Department of Molecular and Cell Biology, University of California, Berkeley, CA 94720, USA
    J Immunol 167:132-9. 2001
    ..These results indicate that ICOS/B7h counterreceptors likely function in vivo to enhance secondary responses by CD8(+) T cells...
  61. ncbi Natural killer cells kill human melanoma cells with characteristics of cancer stem cells
    Gabriella Pietra
    Dipartimento di Medicina Sperimentale and Centro di Eccellenza per la Ricerca Biomedica, Universita degli Studi di Genova, Genova, Italy
    Int Immunol 21:793-801. 2009
    ..Since CSC have been reported to be both drug resistant and radioresistant, our present data suggest that NK-based adoptive immunotherapy could represent a novel therapeutic approach to possibly eradicate metastatic melanoma...
  62. ncbi Modulation of natural killer cell cytotoxicity and cytokine release by the drug glatiramer acetate
    K L Sand
    Department of Physiology, Institute of Basic Medical Sciences, University of Oslo, Norway
    Cell Mol Life Sci 66:1446-56. 2009
    ..Further, GA inhibited the release of IFN-gamma 24 h but increased the release of TNF-alpha 48 h after incubation with NK cells...
  63. ncbi Natural killer cells in antiviral defense: function and regulation by innate cytokines
    C A Biron
    Department of Molecular Microbiology and Immunology, Brown University, Providence, Rhode Island 02912, USA
    Annu Rev Immunol 17:189-220. 1999
    ....
  64. pmc Noncytotoxic functions of NK cells: direct pathogen restriction and assistance to adaptive immunity
    Till Strowig
    Laboratory of Viral Immunobiology and Christopher H Browne Center for Immunology and Immune Diseases, The Rockefeller University, New York, NY 10065, USA
    J Immunol 180:7785-91. 2008
    ..In humans, a dedicated NK cell subset primarily fulfills these later functions. In this review we discuss the noncytotoxic effector functions of NK cells and how they could be harnessed for immunotherapy and vaccine development...
  65. pmc NKp44, a triggering receptor involved in tumor cell lysis by activated human natural killer cells, is a novel member of the immunoglobulin superfamily
    C Cantoni
    Istituto Nazionale per la Ricerca sul Cancro and Centro Biotecnologie Avanzate, 16132 Genova, Italy
    J Exp Med 189:787-96. 1999
    ..Unlike genes coding for other receptors involved in NK cell triggering or inhibition, the NKp44 gene is on human chromosome 6...
  66. ncbi Two distinct pathways of specific killing revealed by perforin mutant cytotoxic T lymphocytes
    H Kojima
    Laboratory of Cellular Immunology, Mitsubishi Kasei Institute of Life Sciences, Tokyo, Japan
    Immunity 1:357-64. 1994
    ..These data not only confirmed the primary role of perforin but simultaneously revealed a major contribution of a perforin-independent Fas-mediated pathway in antigen-specific cytolysis...
  67. ncbi Cutting edge: rapid in vivo CTL activity by polyoma virus-specific effector and memory CD8+ T cells
    Anthony M Byers
    Department of Pathology, Emory University School of Medicine, Atlanta, GA 30322, USA
    J Immunol 171:17-21. 2003
    ..These findings strongly support the concept that a cytotoxic effector-memory CD8(+) T cell population operates in vivo to control this persistent viral infection...
  68. ncbi Phenotypic classification of human CD8+ T cells reflecting their function: inverse correlation between quantitative expression of CD27 and cytotoxic effector function
    Hiroko Tomiyama
    Division of Viral Immunology, Center for AIDS Research, Kumamoto University, Honjo, Kumamoto, Japan
    Eur J Immunol 34:999-1010. 2004
    ..Phenotypic analyses of CD8(+) T cells using this classification will enable the characterization of antigen-specific CD8(+) T cells...
  69. pmc Vav1 dephosphorylation by the tyrosine phosphatase SHP-1 as a mechanism for inhibition of cellular cytotoxicity
    Christopher C Stebbins
    Laboratory of Immunogenetics, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, Maryland 20852, USA
    Mol Cell Biol 23:6291-9. 2003
    ..Such a mechanism explains how inhibitory receptors can block activating signals induced by different receptors...
  70. ncbi Deficient expression of NCR in NK cells from acute myeloid leukemia: Evolution during leukemia treatment and impact of leukemia cells in NCRdull phenotype induction
    Cyril Fauriat
    Laboratoire d Immunologie des Tumeurs, Institut National de la Santé et de la Recherche Médicale INSERM Unite Mixté de Recherche UMR 599, Marseille, France
    Blood 109:323-30. 2007
    ..The prognostic value of NCR expression is discussed, and pathophysiologic implication of the NCR phenotype will be further investigated in a larger study...
  71. pmc Molecular cloning of NKp46: a novel member of the immunoglobulin superfamily involved in triggering of natural cytotoxicity
    A Pessino
    Dipartimento di Medicina Sperimentale, Universita degli Studi di Genova, Italy
    J Exp Med 188:953-60. 1998
    ..In conclusion, this study reports the first characterization of the molecular structure of a NK-specific receptor involved in the mechanism of NK cell activation during natural cytotoxicity...
  72. ncbi Human natural killer cell receptors and co-receptors
    R Biassoni
    Istituto Nazionale per la Ricerca sul Cancro, Genova, Italy
    Immunol Rev 181:203-14. 2001
    ..Future studies will clarify whether also the altered expression and/or function of other NK-triggering molecules may represent a possible cause of immunological disorders...
  73. ncbi Mesenchymal stem cells inhibit natural killer-cell proliferation, cytotoxicity, and cytokine production: role of indoleamine 2,3-dioxygenase and prostaglandin E2
    Grazia Maria Spaggiari
    Centro di Eccellenza per la Ricerca Biomedica, Biologia e Genetica, Universita di Genova, Genova, Italy
    Blood 111:1327-33. 2008
    ..Finally, we demonstrate that indoleamine 2,3-dioxygenase and prostaglandin E2 represent key mediators of the MSC-induced inhibition of NK cells...
  74. ncbi Major histocompatibility complex class I-related chain A and UL16-binding protein expression on tumor cell lines of different histotypes: analysis of tumor susceptibility to NKG2D-dependent natural killer cell cytotoxicity
    Daniela Pende
    Istituto Nazionale per la Ricerca sul Cancro, 16132 Genova, Italy
    Cancer Res 62:6178-86. 2002
    ..Our data suggest that the involvement of NKG2D in natural killer cell-mediated cytotoxicity strictly correlates with the expression and the surface density of MICA and ULBP on target cell tumors of different histotypes...
  75. ncbi Human and mouse granzyme A induce a proinflammatory cytokine response
    Sunil S Metkar
    Department of Medicine, NorthShore University HealthSystem Research Institute, Evanston, IL 60201, USA
    Immunity 29:720-33. 2008
    ..Thus, the granule secretory pathway plays an unexpected role in inflammation, with GzmA acting as an endogenous modulator...
  76. pmc Existence of both inhibitory (p58) and activatory (p50) receptors for HLA-C molecules in human natural killer cells
    A Moretta
    Istiuto Nazionale per la Ricerca sul Cancro, Genova Italy
    J Exp Med 182:875-84. 1995
    ..abstract truncated at 400 words)..
  77. ncbi Rapid CD8+ T cell repertoire focusing and selection of high-affinity clones into memory following primary infection with a persistent human virus: human cytomegalovirus
    Elizabeth K Day
    Department of Medicine, School of Clinical Medicine, Addenbrookes Hospital, Hills Road, Cambridge, United Kingdom
    J Immunol 179:3203-13. 2007
    ..Thus, the oligoclonal T cell repertoire against an immunodominant persistent viral epitope is established early in primary infection by the rapid selection of public clonotypes, rather than being a stochastic process...
  78. pmc Many NK cell receptors activate ERK2 and JNK1 to trigger microtubule organizing center and granule polarization and cytotoxicity
    Xi Chen
    Department of Molecular and Cellular Biology, Harvard University, Cambridge, MA 02138, USA
    Proc Natl Acad Sci U S A 104:6329-34. 2007
    ..By contrast, CD2, DNAM-1, and beta(1)-integrin crosslinking do not activate either pathway; they may be costimulatory molecules or have another function in the synapse...
  79. pmc Immediate cytotoxicity but not degranulation distinguishes effector and memory subsets of CD8+ T cells
    Petra Wolint
    Institute for Microbiology, Eidgenossische Technische Hochschule Zurich, Schmelzbergstrasse 7, 8092, Switzerland
    J Exp Med 199:925-36. 2004
    ..Furthermore, these results provide a potential mechanism by which central memory CD8+ T cell-mediated death of antigen-presenting cells within the lymph node is avoided...
  80. ncbi Killing of human immunodeficiency virus-infected primary T-cell blasts by autologous natural killer cells is dependent on the ability of the virus to alter the expression of major histocompatibility complex class I molecules
    Matthew I Bonaparte
    Department of Microbiology and Immunology, State University of New York, Upstate Medical University, Syracuse, NY 13210, USA
    Blood 104:2087-94. 2004
    ....
  81. ncbi Human NKT cells express granulysin and exhibit antimycobacterial activity
    Jennifer L Gansert
    Division of Hematology and Oncology and Department of Microbiology and Immunology, University of California, Los Angeles, School of Medicine, Los Angeles, CA 90095, USA
    J Immunol 170:3154-61. 2003
    ..These studies provide evidence that alpha Gal Cer-activated CD1d-restricted T cells can participate in human host defense against M. tuberculosis infection...
  82. ncbi Increased susceptibility to tumor initiation and metastasis in TNF-related apoptosis-inducing ligand-deficient mice
    Erika Cretney
    Cancer Immunology Program, Sir Donald and Lady Trescowthick Laboratories, Peter MacCallum Cancer Institute, A Beckett Street, East Melbourne, 8006 Victoria, Australia
    J Immunol 168:1356-61. 2002
    ..TRAIL gene-targeted mice were also more sensitive to the chemical carcinogen methylcholanthrene. These results substantiated TRAIL as an important natural effector molecule used in the host defense against transformed cells...
  83. pmc Intrahepatic IL-10 maintains NKG2A+Ly49- liver NK cells in a functionally hyporesponsive state
    Matthew G Lassen
    Beirne B Carter Center for Immunology Research, Department ofMicrobiology, University of Virginia, Charlottesville, VA 22908, USA
    J Immunol 184:2693-701. 2010
    ....
  84. ncbi Beta 2-microglobulin deficient mice lack CD4-8+ cytolytic T cells
    M Zijlstra
    Whitehead Institute for Biomedical Research, Cambridge, Massachusetts
    Nature 344:742-6. 1990
    ....
  85. ncbi Epstein-Barr nuclear antigen 1-specific CD4(+) Th1 cells kill Burkitt's lymphoma cells
    Casper Paludan
    Laboratory of Cellular Physiology and Immunology, The Rockefeller University, New York, NY 10021, USA
    J Immunol 169:1593-603. 2002
    ..Therefore, adaptive immunity can be directed against Burkitt's lymphoma, and perhaps this role for CD4(+) Th1 cells extends to other tumors that escape MHC class I presentation...
  86. ncbi HIV type 1-infected dendritic cells induce apoptotic death in infected and uninfected primary CD4 T lymphocytes
    Miriam Lichtner
    Antigen Presentation by Dendritic Cell Group, Departement d Immunologie, Institut Cochin, INSERM U567, UMR CNRS 8104, IFR 116 Paris V University, Paris, France
    AIDS Res Hum Retroviruses 20:175-82. 2004
    ..Therefore this new cytotoxic function of DCs may play an important role in innate and adaptive immunity during HIV infection...
  87. ncbi Reconstitution of NK cell receptor repertoire following HLA-matched hematopoietic cell transplantation
    Heather G Shilling
    Department of Structural Biology, Stanford University School of Medicine, Stanford, CA 94305, USA
    Blood 101:3730-40. 2003
    ..These results demonstrate that a majority of HLA-matched hematopoietic cell transplantations involve KIR mismatch and reveal differences in NK cell repertoire having potential impact for immune responsiveness and transplantation outcome...
  88. ncbi Cytotoxic T lymphocytes: all roads lead to death
    Michele Barry
    Department of Medical Microbiology and Immunology, University of Alberta, Edmonton, Canada
    Nat Rev Immunol 2:401-9. 2002
    ..So, an understanding of the mechanisms that are used by CTLs to destroy targets and a knowledge of pathogen immune-evasion strategies will provide vital information for the design of new therapies...
  89. ncbi Cutting edge: induction of IFN-gamma production but not cytotoxicity by the killer cell Ig-like receptor KIR2DL4 (CD158d) in resting NK cells
    S Rajagopalan
    Laboratory of Immunogenetics, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, MD 20852, USA
    J Immunol 167:1877-81. 2001
    ..These results reveal a functional dichotomy (cytokine production vs cytotoxicity) in the response of resting NK cells, as dictated by the signals of individual receptors...
  90. pmc Apoptotic pathways are selectively activated by granzyme A and/or granzyme B in CTL-mediated target cell lysis
    Julian Pardo
    Departmento de Bioquímica y Biología Molecular y Celular, Universidad de Zaragoza, E 50009 Zaragoza, Spain
    J Cell Biol 167:457-68. 2004
    ..The ability of gzmA and gzmB to induce multiple independent cell death pathways may be the hosts response to circumvent evasion strategies of pathogens and tumors...
  91. ncbi Defective expression and function of natural killer cell-triggering receptors in patients with acute myeloid leukemia
    Regis T Costello
    Unité d Immunologie des Tumeurs Département d Hématologie, Institut Paoli Calmettes, Universite de la Mediterranee, Marseille, France
    Blood 99:3661-7. 2002
    ..In few cases, however, this failure appears to involve a mechanism of tumor escape based on down-regulation of ligands relevant for NCR-mediated target cell recognition...
  92. ncbi Natural cytotoxicity receptors that trigger human NK-cell-mediated cytolysis
    A Moretta
    Dipartimento di Medicina Sperimentale, University of Genova, Italy
    Immunol Today 21:228-34. 2000
    ..Here, Alessandro Moretta and colleagues describe the identification and characterization of several such receptors...
  93. ncbi CD56bright cells differ in their KIR repertoire and cytotoxic features from CD56dim NK cells
    R Jacobs
    Department of Clinical Immunology, Hannover Medical School, Hannover, Germany
    Eur J Immunol 31:3121-7. 2001
    ..The poor cytolytic capacity of CD56bright NK cells can be explained by weak ability in forming conjugates with target cells and low contents of perforin and granzyme A in their granules...
  94. ncbi Blockade of B7-H1 improves myeloid dendritic cell-mediated antitumor immunity
    Tyler J Curiel
    Tulane University Health Science Center, New Orleans, Louisiana, USA
    Nat Med 9:562-7. 2003
    ..Therefore, upregulation of B7-H1 on MDCs in the tumor microenvironment downregulates T-cell immunity. Blockade of B7-H1 represents one approach for cancer immunotherapy...
  95. ncbi Protein kinase C delta localizes to secretory lysosomes in CD8+ CTL and directly mediates TCR signals leading to granule exocytosis-mediated cytotoxicity
    Jennifer S Y Ma
    Center for Cancer and Immunology, Children s National Medical Center, Children s Research Institute, Washington, DC 20010, USA
    J Immunol 181:4716-22. 2008
    ....
  96. ncbi The intracellular granzyme B inhibitor, proteinase inhibitor 9, is up-regulated during accessory cell maturation and effector cell degranulation, and its overexpression enhances CTL potency
    Claire E Hirst
    Department of Biochemistry and Molecular Biology, Monash University, Clayton, Australia
    J Immunol 170:805-15. 2003
    ..In conclusion, the presence and subcellular localization of PI-9 in leukocytes and DCs are consistent with a protective role against ectopic or misdirected grB during an immune response...
  97. pmc Evolutionary struggles between NK cells and viruses
    Lewis L Lanier
    Department of Microbiology and Immunology, and the Cancer Research Institute, University of California San Francisco, San Francisco, California 94143 0414, USA
    Nat Rev Immunol 8:259-68. 2008
    ..In addition to their participation in the immediate innate immune response against infection, interactions between NK cells and dendritic cells shape the nature of the subsequent adaptive immune response to pathogens...
  98. ncbi KIR2DL4 (CD158d), an NK cell-activating receptor with inhibitory potential
    Mathias Faure
    Laboratory of Immunogenetics, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, MD 20852, USA
    J Immunol 168:6208-14. 2002
    ..Therefore, KIR2DL4 has inhibitory potential in addition to its activating function...
  99. ncbi A central role for death receptor-mediated apoptosis in the rejection of tumors by NK cells
    V Screpanti
    Department of Immunology, Wenner Gren Institute, University of Stockholm, Stockholm, Sweden
    J Immunol 167:2068-73. 2001
    ..Moreover, our data indicate that death receptor-mediated apoptosis has a more prominent role in the clearance of NK-sensitive tumors than previously suggested...
  100. ncbi Retargeting of natural killer-cell cytolytic activity to ErbB2-expressing cancer cells results in efficient and selective tumor cell destruction
    Christoph Uherek
    Chemotherapeutisches Forschungsinstitut Georg Speyer Haus, Frankfurt am Main, Germany
    Blood 100:1265-73. 2002
    ..These results demonstrate that efficient retargeting of NK-92 cytotoxicity can be achieved and might allow the generation of potent cell-based therapeutics for the treatment of ErbB2-expressing malignancies...
  101. ncbi Good manufacturing practices production of natural killer cells for immunotherapy: a six-year single-institution experience
    David H McKenna
    Department of Laboratory Medicine and Pathology, Division of Transfusion Medicine, University of Minnesota Medical School, Minnesota 55108, USA
    Transfusion 47:520-8. 2007
    ..Herein is a report on the experience of clinical-scale, good manufacturing practices (GMPs) production of NK cells to treat advanced cancer...

Research Grants71

  1. CYTOTOXIC MECHANISMS IN CUTANEOUS DISEASE
    David Norris; Fiscal Year: 2007
    ..major objective of this grant over the past 20 years has been to study key aspects of the mechanisms of immunologic cytotoxicity in skin disease...
  2. Dendritic Cells and Breast Cancer Immunity
    A Palucka; Fiscal Year: 2004
    ..Overall, this proposal will permit us to demonstrate that efficient breast cancer immunity can be generated and used to reject the tumor thus permitting development of novel treatment modalities in breast cancer. ..
  3. Mice with Human Dendritic Cells to Test Vaccine Potency
    A Palucka; Fiscal Year: 2004
    ..The experiments proposed here would lay ground for further use of SCID-hu/DCs mice to study other vaccines and demonstrate development of protective immunity upon in vivo rechallenge. ..
  4. ACTIVITY OF EXPANDED GAMMA/DELTA T CELLS
    Michael Verneris; Fiscal Year: 2005
    ..Thus, the candidate will acquire the skills to secure a faculty position as a pediatric bone marrow transplantation clinical-scientist...
  5. Endogenous MHC class II antigen processing via autophagy
    CHRISTIAN MUNZ; Fiscal Year: 2008
    ..These studies will allow us to understand better how tumors can be detected by the immune system and how we can enhance immune responses to cancer. [unreadable] [unreadable] [unreadable]..
  6. Criteria for Protective Immunity to BK virus in Kidney Transplant Recipients
    Simon Lacey; Fiscal Year: 2007
    ..Information from the proposed study may allow identification of patients at risk of progression from BKV reactivation to clinical BKV disease and guide therapeutic interventions. [unreadable] [unreadable] [unreadable]..
  7. Cellular Immunity to BK Virus
    Simon Lacey; Fiscal Year: 2005
    ..Such information may be useful in guiding clinical management, and lay the foundation for possible future vaccines. ..
  8. Molecular Mechanisms of HIV Disease Pathogenesis
    Kathleen L Collins; Fiscal Year: 2011
    ..This proposal is relevant to the mission of NIH in that it seeks to understand basic mechanisms of how HIV establishes a chronic infection. This work has the potential to have a significant impact on public health. ..
  9. BIOLOGY OF HUMAN INTRAEPITHELIAL LYMPHOCYTES
    Ellen Ebert; Fiscal Year: 2002
    ..These studies will determine the mechanism of IEL chemotaxis toward secreted products of ECs, why IL-15 is more potent than IL-2 in inducing LAK activity by IELs, and how IL-10 and IL-12 augment this activity. ..
  10. The regulation of tumor immunity by NKT cells
    Mark Smyth; Fiscal Year: 2007
    ..This proposal focuses clearly on a pivotal immune control mechanism that will influence many current and future immunotherapies. ..
  11. Mechanisms of NK Cell Activation by the KIR2DL4 Receptor
    Kerry Campbell; Fiscal Year: 2008
    ..What are the molecular mechanisms by which KIR2DL4 transduces unique activation signals inhuman NK cells? ..
  12. Neuropeptide Y and dipeptidyl-peptidase IV (CD26) in chronic fatigue syndrome
    Mary Fletcher; Fiscal Year: 2007
    ..Specific Aim 3 is to define the relationship of NPY and CD26 to NKCC in CFS. Specific Aim 4 is to determine the relationship of NPY and CD26 to clinical severity in CFS patients. [unreadable] [unreadable] [unreadable]..
  13. Analysis of serum folate receptor and antibody level for ovarian cancer detection
    Keith Knutson; Fiscal Year: 2007
    ..unreadable] [unreadable] [unreadable]..
  14. Developing RNA Interference for and HIV microbicide
    Judy Lieberman; Fiscal Year: 2005
    ..test siRNA delivery strategies in the human skin blister model; 3. test siRNAs and siRNA delivery strategies for silencing SIV gag and CCR5 in PBMCs from pig-tailed macaques. ..
  15. Neurokinin-1R (SP Receptor) Antagonists for HIV Therapy
    Steven Douglas; Fiscal Year: 2008
    ....
  16. CD4 T cell Dependent Acute Cardiac Allograft Rejection
    Biagio Pietra; Fiscal Year: 2004
    ..The information obtained will be useful in understanding the basic immune mechanisms of human cardiac transplantation. ..
  17. DENVER AUTOIMMUNITY CENTER OF EXCELLENCE
    V Holers; Fiscal Year: 2007
    ..This latter project involves a newly established collaboration with a separate institution and group of clinicians skilled in the clinical investigation of RA. ..
  18. FASEB Research Conference: Lymphocytes and Antibodies
    Leo Lefrancois; Fiscal Year: 2004
    ..In Vivo T Cell Activation - Marc Jenkins (UMINN), Session Organizer 9. Cytokine Control of Immunity - Leo Lefrancois (UCHC), Session Organizer ..
  19. Chemokine and antigen-carrying nanoparticle co-delivery for an oral HIV vaccine
    DARRELL IRVINE; Fiscal Year: 2008
    ..unreadable] [unreadable] [unreadable]..
  20. Eosinophil Recruitment and Activation in Solid Tumors
    James Lee; Fiscal Year: 2009
    ..e., the release of toxic cationic secondary granule proteins) has direct effects on mammary gland tumors. ..
  21. Mechanism of perforin activity
    Judy Lieberman; Fiscal Year: 2010
    ..Structural studies will focus on the perforin C2 domain, hypothesized to undergo a structural change in response to binding Ca++, which is likely to be the first step in membrane binding and insertion. ..
  22. Imaging proteolytic activity in colon cancer
    Khashayarsha Khazaie; Fiscal Year: 2008
    ..These preclinical studies will prepare the grounds for near future clinical trials. ..
  23. Transgenic B-Cell Immunogenes
    Maurizio Zanetti; Fiscal Year: 2002
    ....
  24. Control of CD4+ T cell Islet Entry and Diabetogenicity
    Dario Vignali; Fiscal Year: 2008
    ..to track the kinetics of islet entry, the role of islet-resident DCs and B cells, and the contribution of Tregs in modulating T cell diabetogenic potential. ..
  25. ANTITUMOR IMMUNITY INDUCED BY FUSION CELLS VACCINATION
    Jianlin Gong; Fiscal Year: 2003
    ..3). To assess the effectiveness of fusion cell vaccines in the prevention and treatment of spontaneous breast carcinoma in transgenic mice. ..
  26. Immunochaperone-based gene therapy targeting prostate cancer
    Xiang yang Wang; Fiscal Year: 2007
    ..The proposed research could lead to the design of a clinical trial for patients with prostate cancer in the very near future. [unreadable] [unreadable] [unreadable]..
  27. CD8+ T CELLS AND MYCOPLASMA TUBERCULOSIS
    DAVID CANADAY; Fiscal Year: 2003
    ..Aim 3. To characterize the functional CD8+ T cell responses to specific proteins and peptides from in patients with active M. tuberculosis infection. ..
  28. DEVELOPMENT AND PERSISTENCE OF MEMORY T LYMPHOCYTES
    Philip Ashton Rickardt; Fiscal Year: 2009
    ..The research proposed will lead to improved in vaccination through the induction of potent T cell memory, a goal that up until now has remained elusive for many viruses and cancers. ..
  29. ADAPTOR PROTEINS REGULATING B CELL MATURATION
    Edward Clark; Fiscal Year: 2004
    ..We will generate first GrpL-/-mice and then BAM32-/- mice, and test if GrpL-/- or BAM-32-/- mice have defective lymphoid development or responses to Ag. ..
  30. METHODS TO ENHANCE IMMUNOTHERAPY OF HEAD AND NECK CANCER
    Scott Strome; Fiscal Year: 2004
    ..abstract_text> ..
  31. Dendritic cells, Mucosal Immunity and C-type Lectins
    Edward Clark; Fiscal Year: 2009
    ..gingivalis as measured by alveolar bone loss and antibody responses. This work will lead to better understanding about how microflora can affect DCs. ..
  32. Real-time Imaging of Immune Cell-Tumor Cell Interactions
    Wolfgang Weninger; Fiscal Year: 2007
    ..The implication of this research is that an in-depth understanding of immune cell-tumor cell communication will, in the long-term, help to generate improved cellular immuno-therapeutic approaches. [unreadable] [unreadable]..
  33. Immune Control of HIV in Children
    Margaret Feeney; Fiscal Year: 2006
    ..This research will be conducted under the guidance of leading investigators in the field of HIV immunopathogenesis in adults. ..
  34. Dissecting lymphocyte chemotaxis using synthetic chemokine-releasing microspheres
    DARRELL IRVINE; Fiscal Year: 2009
    ..These results will have implications for understanding how trafficking in the immune system is regulated and will shed light on how chemokines might be targeted to inhibit or enhance ectopic lymphoid tissue formation for immunotherapy. ..
  35. Regulation of human microRNA biosynthesis and activity
    BRYAN CULLEN; Fiscal Year: 2007
    ..Finally, in specific aim 5, we seek to extend our exciting initial data demonstrating inhibition of miRNA function by the adenovirus VA1 non-coding RNA by trying to define the underlying mechanism. ..
  36. Ex vivo expansion of HER-2/neu specific T helper cells
    Keith Knutson; Fiscal Year: 2008
    ..abstract_text> ..
  37. Interferon-Producing Killer Dendritic Cells in Anti-Viral Immunity
    CAMIE CHAN; Fiscal Year: 2008
    ..unreadable] [unreadable] [unreadable]..
  38. HLA classl complex expression in breast cancer immunity
    Keith Knutson; Fiscal Year: 2009
    ..The results will likely lead to the identification of specific molecule associated with antigen presentation that could be either a novel therapeutic target or biomarker of disease outcome. ..
  39. Sex in Myocarditis
    Sally Huber; Fiscal Year: 2008
    ..By understanding the factors controlling virus infection and induction of innate immunity, better mechanism for controlling viral disease should be possible. ..
  40. MOLECULAR MODEL FOR T-CELL RECEPTOR LIGAND INTERACTIONS
    Nilabh Shastri; Fiscal Year: 2007
    ..We expect the findings to reveal new insights into the nature of endogenous peptides presented by MHC class II and MHC class I molecules in normal cells as well as fundamental issues in transplantation immunology. ..
  41. Immune Defense: The Role of NKG2D/DAP10
    Marco Colonna; Fiscal Year: 2007
    ..abstract_text> ..
  42. Intradermal vaccinia:T-cell specificity and skin homing
    David Koelle; Fiscal Year: 2005
    ..2) Measure E-selectin binding by vaccinia-specific CD8 cells, and 2.3) Compare CLA and E-selectin binding by vaccinia-specific T-cells in recent and distant vaccines. ..
  43. MULTIDISCIPLINARY TRAINING IN EXPERIMENTAL HEMATOLOGY
    Scott Kaufmann; Fiscal Year: 2005
    ..This program is a natural outgrowth of existing training opportunities in hematology, but will provide better preparation for laboratory research in hematological diseases. (End of Abstract) ..
  44. NK AND T CELL COSTIMULATION BY NKG2D/DAP10
    LEWIS LANIER; Fiscal Year: 2005
    ..Given the broad distribution of MICA/B on freshly isolated human tumors, studies of the NKG2D-DAP10 receptor may provide new opportunities for immunotherapeutic intervention in cancer. ..
  45. Role of IL18 in Spread of Prostate Cancer to Bone
    Pamela Russell; Fiscal Year: 2004
    ..If IL18 inhibits PCa growth in bone, its delivery by adenovirus vectors into the prostate of patients prior to radical prostatectomy may prevent the development of bone metastasis. ..
  46. ONTOGENY OF RSV-SPECIFIC B CELL RESPONSES IN HUMANS
    James Crowe; Fiscal Year: 2001
    ..The data from this work will direct decisions about the best vaccine strategy to use against RSV in neonates, and will delineate basic mechanisms of the ontogeny of B-cell repertoire diversity in humans. ..
  47. A Zeiss LSM 510 Confocal Microscope for Medical Research
    Ruth Montgomery; Fiscal Year: 2004
    ..Thus this confocal microscope would be the basis of a core facility to assure that these investigators will have adequate access to state-of-the-art imaging techniques. ..
  48. Vulnerability to Smallpox Due to Declining CTL Immunity
    Innocent Mbawuike; Fiscal Year: 2003
    ..By correlating these responses with vaccinia lesion sizes in new vaccinees, markers of severe complications from vaccinia vaccination may be identified. ..
  49. FUNCTION & HOMEOSTASIS OF VIRAL PATHOGEN-SPECIFIC CD4+
    Louis Picker; Fiscal Year: 2002
    ..abstract_text> ..
  50. HIV-1 TROPISM AND CHEMOKINE RECEPTORS
    BRYAN CULLEN; Fiscal Year: 2002
    ..The final specific aim focusses on the promoter regions of CCR5, the identification of transcription factors that may interact with the promoter, and the use of antisense strategies to block CCR5 expression. ..
  51. FACSVantage SE
    Beth Jamieson; Fiscal Year: 2002
    ..The FCCF staff will continue to develop and adapt novel technologies for use with the new instrument to support UCLA investigators in their efforts to remain on the cutting edge of science. ..
  52. Novel methods for generation of human B cell hybridomas
    James Crowe; Fiscal Year: 2005
    ..abstract_text> ..
  53. Two-photon Microscope System for In-vivo Imaging
    Wolfgang Weninger; Fiscal Year: 2006
    ..It is anticipated that the instrument will help to obtain novel insights into the pathomechanisms of disease, including autoimmunity, cancer, and chronic infections. [unreadable] [unreadable] [unreadable]..
  54. MULTICENTER AIDS COHORT STUDY PATHOGENESIS RESEARCH LABS
    Beth Jamieson; Fiscal Year: 2003
    ....
  55. Lyso-PCs activate PMNs and endothelium via PKC
    CHRISTOPHER SILLIMAN; Fiscal Year: 2006
    ..Completion of these specific aims will likely result in targets for in vitro, and possibly clinical, intervention to develop methods to inhibit or to attenuate the effects of these lipids and ultimately make transfusion safer. ..
  56. CD8+T cell responses to Chlamydia pneumoniae
    Benjamin Wizel; Fiscal Year: 2006
    ..pneumoniae and will suggest methods of immunological intervention in infections caused by C. pneumoniae and other chlamydial pathogens. ..
  57. Inflammation and T cell immunity to Listeria
    Eric Pamer; Fiscal Year: 2006
    ..Our studies will shed light on the important interactions between innate immunity and adaptive T cell responses. ..
  58. Mechanisms of Radiation Induced Fatigue in Cancer
    Julienne Bower; Fiscal Year: 2006
    ..Together with a targeted program of didactic instruction, this project will prepare the candidate to become a fully independent behavioral scientist in the field of cancer prevention and control research. ..
  59. Granulysin: A Novel Cytolytic Molecule
    David Lewis; Fiscal Year: 2006
    ..The ultimate goal of these studies is to use granulysin, peptide components, and/or the information gained from the mechanistic studies to develop new antibiotics and/or tumor chemotherapeutic agents. ..
  60. Influence of Lactation on Postpartum Stress and Immunity
    MAUREEN EDITH GROER; Fiscal Year: 2010
    ..The immunology and endocrinology of the postpartum provides a lens through which to study autoimmune disease, as the postpartum is a critical period for development or exacerbation of many autoimmune diseases. ..
  61. Granzyme a Pathway of CTL-Mediated Cell Death
    Judy Lieberman; Fiscal Year: 2008
    ..abstract_text> ..
  62. Recruitment of memory CD8+ T cells to the lung airways
    JACOB KOHLMEIER; Fiscal Year: 2007
    ..unreadable] [unreadable] [unreadable]..
  63. MECHANISMS FOR FORMATION OF CELL MEMBRANE DOMAINS
    Michael Edidin; Fiscal Year: 2002
    ..The PI proposes to test his model using cells in which the barriers to lateral mobility are defective, sph/sph, alpha-spectrin-deficient, erythroleukemia cells, and cells in which vesicle traffic from and to the surface is inhibited. ..
  64. NEUROENDOCRINE IMMUNE CORRELATES OF SELF ADMINISTERED HE
    Richard Weber; Fiscal Year: 2003
    ..These studies may provide avenues for novel treatments where opiatergic systems are implicated in HIV infection and the high incidence of AIDS in intravenous heroin users. ..
  65. MECHANISM OF ANTICARCINOGENIC ACTIVITY--ORGANOSULFIDES
    Shivendra Singh; Fiscal Year: 2003
    ..Insights gained from these studies should help in devising practical dietary recommendation for humans. ..
  66. CD19-Specific T-Cell Therapy for Follicular Lymphoma
    LAURENCE COOPER; Fiscal Year: 2004
    ....
  67. NOVEL GST AND DETOXICATION OF DIOL EPOXIDES
    Shivendra Singh; Fiscal Year: 2006
    ..In the long-term, this knowledge will guide us in developing strategies for prevention of PAH-induced cancers in humans. ..
  68. Anti-CTLA-4 Monoclonal Antibody Therapy for Lymphoma
    John Timmerman; Fiscal Year: 2005
    ..abstract_text> ..
  69. Allogeneic T Cell Responses Against Renal Cell Carcinoma
    Edus Warren; Fiscal Year: 2008
    ..3) Identify the genes encoding antigens recognized by RCC-reactive CD8+ T cell clones isolated from patients with metastatic RCC who exhibit tumor regression after nonmyeloablative HCT. ..