helper inducer t lymphocytes

Summary

Summary: Subpopulation of CD4+ lymphocytes that cooperate with other lymphocytes (either T or B) to initiate a variety of immune functions. For example, helper-inducer T-cells cooperate with B-cells to produce antibodies to thymus-dependent antigens and with other subpopulations of T-cells to initiate a variety of cell-mediated immune functions.

Top Publications

  1. ncbi The orphan nuclear receptor RORgammat directs the differentiation program of proinflammatory IL-17+ T helper cells
    Ivaylo I Ivanov
    Molecular Pathogenesis Program, Skirball Institute of Biomolecular Medicine, New York University School of Medicine, 540 First Avenue, New York, NY 10016, USA
    Cell 126:1121-33. 2006
  2. pmc A distinct lineage of CD4 T cells regulates tissue inflammation by producing interleukin 17
    Heon Park
    Department of Immunology, University of Washington, Seattle, Washington 98195, USA
    Nat Immunol 6:1133-41. 2005
  3. pmc IL-21 initiates an alternative pathway to induce proinflammatory T(H)17 cells
    Thomas Korn
    Center for Neurologic Diseases, Brigham and Women s Hospital, Harvard Medical School, Boston, Massachusetts 02115, USA
    Nature 448:484-7. 2007
  4. ncbi IL-6 programs T(H)-17 cell differentiation by promoting sequential engagement of the IL-21 and IL-23 pathways
    Liang Zhou
    The Kimmel Center for Biology and Medicine of the Skirball Institute, New York University School of Medicine, New York, New York 10016, USA
    Nat Immunol 8:967-74. 2007
  5. ncbi Interleukin-22, a T(H)17 cytokine, mediates IL-23-induced dermal inflammation and acanthosis
    Yan Zheng
    Department of Immunology, Genentech, Inc, South San Francisco, California 94080, USA
    Nature 445:648-51. 2007
  6. ncbi Interleukin-2 signaling via STAT5 constrains T helper 17 cell generation
    Arian Laurence
    Molecular Immunology and Inflammation Branch, National Institute of Arthritis, Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, MD 20892, USA
    Immunity 26:371-81. 2007
  7. ncbi Development, cytokine profile and function of human interleukin 17-producing helper T cells
    Nicholas J Wilson
    Department of Discovery Research, Schering Plough Biopharma Formerly DNAX Research, Palo Alto, California 94304 1104, USA
    Nat Immunol 8:950-7. 2007
  8. ncbi Interleukins 1beta and 6 but not transforming growth factor-beta are essential for the differentiation of interleukin 17-producing human T helper cells
    Eva V Acosta-Rodriguez
    Institute for Research in Biomedicine, CH 6500 Bellinzona, Switzerland
    Nat Immunol 8:942-9. 2007
  9. ncbi Interleukin 17-producing CD4+ effector T cells develop via a lineage distinct from the T helper type 1 and 2 lineages
    Laurie E Harrington
    Department of Pathology, University of Alabama at Birmingham, Birmingham, Alabama 35294, USA
    Nat Immunol 6:1123-32. 2005
  10. ncbi TH1 and TH2 cells: different patterns of lymphokine secretion lead to different functional properties
    T R Mosmann
    DNAX Research Institute, Palo Alto, California 94304
    Annu Rev Immunol 7:145-73. 1989

Detail Information

Publications319 found, 100 shown here

  1. ncbi The orphan nuclear receptor RORgammat directs the differentiation program of proinflammatory IL-17+ T helper cells
    Ivaylo I Ivanov
    Molecular Pathogenesis Program, Skirball Institute of Biomolecular Medicine, New York University School of Medicine, 540 First Avenue, New York, NY 10016, USA
    Cell 126:1121-33. 2006
    ..Together, these studies suggest that RORgammat is a key regulator of immune homeostasis and highlight its potential as a therapeutic target in inflammatory diseases...
  2. pmc A distinct lineage of CD4 T cells regulates tissue inflammation by producing interleukin 17
    Heon Park
    Department of Immunology, University of Washington, Seattle, Washington 98195, USA
    Nat Immunol 6:1133-41. 2005
    ..Thus, IL-17 expression characterizes a unique T helper lineage that regulates tissue inflammation...
  3. pmc IL-21 initiates an alternative pathway to induce proinflammatory T(H)17 cells
    Thomas Korn
    Center for Neurologic Diseases, Brigham and Women s Hospital, Harvard Medical School, Boston, Massachusetts 02115, USA
    Nature 448:484-7. 2007
    ..We show that an IL-2 cytokine family member, IL-21, cooperates with TGF-beta to induce T(H)17 cells in naive Il6-/- T cells and that IL-21-receptor-deficient T cells are defective in generating a T(H)17 response...
  4. ncbi IL-6 programs T(H)-17 cell differentiation by promoting sequential engagement of the IL-21 and IL-23 pathways
    Liang Zhou
    The Kimmel Center for Biology and Medicine of the Skirball Institute, New York University School of Medicine, New York, New York 10016, USA
    Nat Immunol 8:967-74. 2007
    ..IL-6 therefore orchestrates a series of 'downstream' cytokine-dependent signaling pathways that, in concert with TGF-beta, amplify RORgammat-dependent differentiation of T(H)-17 cells...
  5. ncbi Interleukin-22, a T(H)17 cytokine, mediates IL-23-induced dermal inflammation and acanthosis
    Yan Zheng
    Department of Immunology, Genentech, Inc, South San Francisco, California 94080, USA
    Nature 445:648-51. 2007
    ..IL-22, as an effector cytokine produced by T cells, mediates the crosstalk between the immune system and epithelial cells...
  6. ncbi Interleukin-2 signaling via STAT5 constrains T helper 17 cell generation
    Arian Laurence
    Molecular Immunology and Inflammation Branch, National Institute of Arthritis, Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, MD 20892, USA
    Immunity 26:371-81. 2007
    ..We conclude that in addition to the promotion of activation-induced cell death of lymphocytes and the generation of Treg cells, inhibition of Th17 polarization appears to be an important function of IL-2...
  7. ncbi Development, cytokine profile and function of human interleukin 17-producing helper T cells
    Nicholas J Wilson
    Department of Discovery Research, Schering Plough Biopharma Formerly DNAX Research, Palo Alto, California 94304 1104, USA
    Nat Immunol 8:950-7. 2007
    ..Our data collectively indicate that human and mouse T(H)-17 cells require distinct factors during differentiation and that human T(H)-17 cells may regulate innate immunity in epithelial cells...
  8. ncbi Interleukins 1beta and 6 but not transforming growth factor-beta are essential for the differentiation of interleukin 17-producing human T helper cells
    Eva V Acosta-Rodriguez
    Institute for Research in Biomedicine, CH 6500 Bellinzona, Switzerland
    Nat Immunol 8:942-9. 2007
    ....
  9. ncbi Interleukin 17-producing CD4+ effector T cells develop via a lineage distinct from the T helper type 1 and 2 lineages
    Laurie E Harrington
    Department of Pathology, University of Alabama at Birmingham, Birmingham, Alabama 35294, USA
    Nat Immunol 6:1123-32. 2005
    ..These findings provide a basis for understanding how inhibition of IFN-gamma signaling enhances development of pathogenic T(H)-17 effector cells that can exacerbate autoimmunity...
  10. ncbi TH1 and TH2 cells: different patterns of lymphokine secretion lead to different functional properties
    T R Mosmann
    DNAX Research Institute, Palo Alto, California 94304
    Annu Rev Immunol 7:145-73. 1989
  11. pmc Generation of T follicular helper cells is mediated by interleukin-21 but independent of T helper 1, 2, or 17 cell lineages
    Roza I Nurieva
    Department of Immunology, University of Texas MD Anderson Cancer Center and Graduate School of Biomedical Sciences, Houston, TX 77030, USA
    Immunity 29:138-49. 2008
    ..This study thus demonstrates that Tfh is a distinct Th cell lineage...
  12. pmc Preferential recruitment of CCR6-expressing Th17 cells to inflamed joints via CCL20 in rheumatoid arthritis and its animal model
    Keiji Hirota
    Department of Experimental Pathology, Institute for Frontier Medical Sciences, Kyoto University, Kyoto 606 8507, Japan
    J Exp Med 204:2803-12. 2007
    ..These results indicate that CCR6 expression contributes to Th17 cell function in autoimmune disease, especially in autoimmune arthritis such as RA...
  13. pmc IL-21 and TGF-beta are required for differentiation of human T(H)17 cells
    Li Yang
    Division of Molecular Immunology, Center for Neurologic Diseases, Brigham and Women s Hospital, Harvard Medical School, Boston, Massachusetts 02115, USA
    Nature 454:350-2. 2008
    ..These data will allow the investigation of this new population of T(H)17 cells in human inflammatory disease...
  14. ncbi Interleukins 27 and 6 induce STAT3-mediated T cell production of interleukin 10
    Jason S Stumhofer
    Department of Pathobiology, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA
    Nat Immunol 8:1363-71. 2007
    ..This effect was dependent on the transcription factors STAT1 and STAT3 for IL-27 and on STAT3 for IL-6. Our studies identify a previously unknown pathway that allows the immune system to temper inflammatory responses...
  15. pmc Impaired T(H)17 cell differentiation in subjects with autosomal dominant hyper-IgE syndrome
    Joshua D Milner
    Laboratory of Immunology, National Institutes of Health, Bethesda, Maryland 20892, USA
    Nature 452:773-6. 2008
    ..Thus, our data suggest that the inability to produce T(H)17 cells is a mechanism underlying the susceptibility to the recurrent infections commonly seen in HIES...
  16. pmc Follicular B helper T cells express CXC chemokine receptor 5, localize to B cell follicles, and support immunoglobulin production
    D Breitfeld
    Molecular Tumor and Immunogenetics, Max Delbruck Center for Molecular Medicine, 13092 Berlin, Germany
    J Exp Med 192:1545-52. 2000
    ..Based on the characteristic localization within secondary lymphoid organs, we suggest to term these cells "follicular B helper T cells" (T(FH))...
  17. pmc Two types of mouse T helper cell. IV. Th2 clones secrete a factor that inhibits cytokine production by Th1 clones
    D F Fiorentino
    Department of Immunology, DNAX Research Institute, Palo Alto, California 94304
    J Exp Med 170:2081-95. 1989
    ..The potential role of CSIF in crossregulation of Th1 and Th2 responses is discussed...
  18. ncbi Reciprocal TH17 and regulatory T cell differentiation mediated by retinoic acid
    Daniel Mucida
    La Jolla Institute for Allergy and Immunology, 9420 Athena Circle, La Jolla, CA 92037, USA
    Science 317:256-60. 2007
    ..These findings indicate that a common metabolite can regulate the balance between pro- and anti-inflammatory immunity...
  19. ncbi Human TH17 lymphocytes promote blood-brain barrier disruption and central nervous system inflammation
    Hania Kebir
    Neuroimmunology Unit, Center for the Study of Brain Diseases, Centre Hospitalier de l Université de Montréal Notre Dame Hospital, 1560 Sherbrooke Street East, Montreal, Quebec H2L 4M1, Canada
    Nat Med 13:1173-5. 2007
    ..Furthermore, T(H)17 lymphocytes transmigrate efficiently across BBB-ECs, highly express granzyme B, kill human neurons and promote central nervous system inflammation through CD4+ lymphocyte recruitment...
  20. ncbi T(H)-17 cells in the circle of immunity and autoimmunity
    Estelle Bettelli
    Center for Neurologic Diseases, Brigham and Women s Hospital, Boston, Massachusetts 02115, USA
    Nat Immunol 8:345-50. 2007
    ..Emerging data regarding T(H)-17 cells suggest a very important function for this T cell subset in immunity and disease...
  21. ncbi TH17 cells in development: an updated view of their molecular identity and genetic programming
    Chen Dong
    Department of Immunology, MD Anderson Cancer Center, Houston, Texas 77030, USA
    Nat Rev Immunol 8:337-48. 2008
    ....
  22. ncbi Surface phenotype and antigenic specificity of human interleukin 17-producing T helper memory cells
    Eva V Acosta-Rodriguez
    Institute for Research in Biomedicine, CH 6500 Bellinzona, Switzerland
    Nat Immunol 8:639-46. 2007
    ..Our results demonstrate that human T(H)-17 cells have distinct migratory capacity and antigenic specificities and establish a link between microbial products, T helper cell differentiation and homing in response to fungal antigens...
  23. pmc Follicular helper T cells are required for systemic autoimmunity
    Michelle A Linterman
    Division of Immunology and Genetics, The John Curtin School of Medical Research, Australian National University, Canberra, ACT 2601, Australia
    J Exp Med 206:561-76. 2009
    ..In contrast, adoptive transfer of sanroque T(FH) cells led to spontaneous GC formation. These findings identify T(FH) dysfunction within GCs and aberrant positive selection as a pathway to systemic autoimmunity...
  24. ncbi Th17 cell differentiation: the long and winding road
    Mandy J McGeachy
    Schering Plough Biopharma, 901 California Avenue, Palo Alto, CA 94304, USA
    Immunity 28:445-53. 2008
    ..Unresolved controversies in this field are also discussed: For example, IL-23 is absolutely required for disease pathogenesis in many models of Th17-cell-mediated autoimmunity, yet its role in Th17 cell development is relatively unclear...
  25. ncbi Interleukin 27 negatively regulates the development of interleukin 17-producing T helper cells during chronic inflammation of the central nervous system
    Jason S Stumhofer
    Department of Pathobiology, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, Pennsylvania 19104 6008, USA
    Nat Immunol 7:937-45. 2006
    ..Thus IL-27, a potent inhibitor of T(H)-17 cell development, may be a useful target for treating inflammatory diseases mediated by these cells...
  26. pmc Deficiency of Th17 cells in hyper IgE syndrome due to mutations in STAT3
    Cindy S Ma
    Immunology and Inflammation Program, Garvan Institute of Medical Research, Darlinghurst 2010, Australia
    J Exp Med 205:1551-7. 2008
    ..Furthermore, they underscore the importance of Th17 responses in normal host defense against the common pathogens S. aureus and C. albicans...
  27. ncbi Interleukin 27 limits autoimmune encephalomyelitis by suppressing the development of interleukin 17-producing T cells
    Marcel Batten
    Department of Molecular Biology, Genentech, South San Francisco, California 94080, USA
    Nat Immunol 7:929-36. 2006
    ..Finally, IL-27 suppressed IL-6-mediated T cell proliferation. These data provide a mechanistic explanation for the IL-27-mediated immune suppression noted in several in vivo models of inflammation...
  28. pmc Regulation of the interleukin (IL)-12R beta 2 subunit expression in developing T helper 1 (Th1) and Th2 cells
    S J Szabo
    Department of Pathology, Washington University School of Medicine, St Louis, Missouri 63110, USA
    J Exp Med 185:817-24. 1997
    ..Thus, IFN-gamma may prevent early Th cells from premature commitment to the Th2 pathway. Controlling the expression of the IL-12R beta 2 subunit could be an important therapeutic target for the redirection of ongoing Th cell responses...
  29. ncbi An essential function for the nuclear receptor RORgamma(t) in the generation of fetal lymphoid tissue inducer cells
    Gerard Eberl
    Molecular Pathogenesis Program, Skirball Institute of Biomolecular Medicine, New York University School of Medicine, New York, New York 10016, USA
    Nat Immunol 5:64-73. 2004
    ..This early LTi cell-mediated activation of lymph node and Peyer's patch mesenchyma forms the necessary platform for the subsequent development of mature lymphoid tissues...
  30. ncbi C-C chemokine receptor 6-regulated entry of TH-17 cells into the CNS through the choroid plexus is required for the initiation of EAE
    Andrea Reboldi
    Institute for Research in Biomedicine, Bellinzona, Switzerland
    Nat Immunol 10:514-23. 2009
    ..Our results identify distinct molecular requirements and ports of lymphocyte entry into uninflamed versus inflamed CNS and suggest that the CCR6-CCL20 axis in the choroid plexus controls immune surveillance of the CNS...
  31. pmc T helper 17 lineage differentiation is programmed by orphan nuclear receptors ROR alpha and ROR gamma
    Xuexian O Yang
    Department of Immunology, M D Anderson Cancer Center, Houston, TX 77030, USA
    Immunity 28:29-39. 2008
    ..Therefore, Th17 differentiation is directed by two lineage-specific nuclear receptors, ROR alpha and ROR gamma...
  32. ncbi A conditioned dendritic cell can be a temporal bridge between a CD4+ T-helper and a T-killer cell
    J P Ridge
    Ghost Lab, Section on T cell Tolerance and Memory, Laboratory of Cellular and Molecular Immunology, NIAID NIH, Bethesda, Maryland 20892, USA
    Nature 393:474-8. 1998
    ....
  33. ncbi T follicular helper (TFH) cells in normal and dysregulated immune responses
    Cecile King
    Immunology and Inflammation Research Program, Garvan Institute of Medical Research, Sydney, NSW 2010, Australia
    Annu Rev Immunol 26:741-66. 2008
    ..Consequently, dysregulation of T(FH) cell function, and over- or under-expression of T(FH) cell-associated molecules such as ICOS or IL-21, most likely contributes to the pathogenesis of certain autoimmune diseases or immunodeficiencies...
  34. pmc Defective CD8 T cell memory following acute infection without CD4 T cell help
    Joseph C Sun
    Department of Immunology and the Howard Hughes Medical Institute, University of Washington, Seattle, WA 98195, USA
    Science 300:339-42. 2003
    ..The results highlight a previously undescribed role for CD4 help in promoting protective CD8 memory development...
  35. ncbi Syk- and CARD9-dependent coupling of innate immunity to the induction of T helper cells that produce interleukin 17
    Salome Leibundgut-Landmann
    Immunobiology Laboratory, Cancer Research UK, London Research Institute, Lincoln s Inn Fields Laboratories, London WC2A 3PX, UK
    Nat Immunol 8:630-8. 2007
    ..Our data indicate that signaling through Syk and CARD9 can couple innate to adaptive immunity independently of Toll-like receptor signals and that CARD9 is required for the development of T(H)-17 responses to some pathogens...
  36. pmc The function of follicular helper T cells is regulated by the strength of T cell antigen receptor binding
    Nicolas Fazilleau
    Department of Immunology and Microbial Sciences, La Jolla, California, USA
    Nat Immunol 10:375-84. 2009
    ..Our studies demonstrate a central function for differences in the binding strength of the T cell antigen receptor in the antigen-specific mechanisms that 'program' specialized effector T(FH) function in vivo...
  37. ncbi Essential autocrine regulation by IL-21 in the generation of inflammatory T cells
    Roza Nurieva
    Department of Immunology, M D Anderson Cancer Center, Houston, Texas 77030, USA
    Nature 448:480-3. 2007
    ..IL-21 is therefore an autocrine cytokine that is sufficient and necessary for T(H)17 differentiation, and serves as a target for treating inflammatory diseases...
  38. pmc T cell self-reactivity forms a cytokine milieu for spontaneous development of IL-17+ Th cells that cause autoimmune arthritis
    Keiji Hirota
    Department of Experimental Pathology, Institute for Frontier Medical Sciences, Kyoto University, Kyoto 606 8507, Japan
    J Exp Med 204:41-7. 2007
    ..Extrinsic or intrinsic stimuli further expand these cells, thereby triggering autoimmune disease. Intervention in these events at cellular and molecular levels is useful to treat and prevent autoimmune disease, in particular RA...
  39. ncbi Cytokine-mediated regulation of human B cell differentiation into Ig-secreting cells: predominant role of IL-21 produced by CXCR5+ T follicular helper cells
    Vanessa L Bryant
    Garvan Institute of Medical Research, Darlinghurst, New South Wales, Australia
    J Immunol 179:8180-90. 2007
    ..These findings suggest that IL-21 produced by TFH cells during the primary as well as the subsequent responses to T cell-dependent Ag makes a major contribution to eliciting and maintaining long-lived humoral immunity...
  40. pmc The biological functions of T helper 17 cell effector cytokines in inflammation
    Wenjun Ouyang
    Department of Immunology, Genentech, 1 DNA Way, South San Francisco, California 94080, USA
    Immunity 28:454-67. 2008
    ..The effector cytokines of Th17 cells, therefore, mediate the crucial crosstalk between immune system and tissues, and play indispensable roles in tissue immunity...
  41. pmc Molecular antagonism and plasticity of regulatory and inflammatory T cell programs
    Xuexian O Yang
    Department of Immunology, M D Anderson Cancer Center, Houston, TX 77030, USA
    Immunity 29:44-56. 2008
    ..STAT3 regulated Foxp3 downregulation, whereas STAT3, RORgamma, and ROR* were required for IL-17 expression in Treg cells. Our data demonstrate molecular antagonism and plasticity of Treg and Th17 cell programs...
  42. pmc Th17 cells promote pancreatic inflammation but only induce diabetes efficiently in lymphopenic hosts after conversion into Th1 cells
    Natalia Martin-Orozco
    Department of Immunology, MD Anderson Cancer Center, Houston, TX 77030, USA
    Eur J Immunol 39:216-24. 2009
    ..These results indicate that islet-reactive Th17 cells promote pancreatic inflammation, but only induce IDDM upon conversion into IFN-gamma producers...
  43. ncbi Control of T(reg) and T(H)17 cell differentiation by the aryl hydrocarbon receptor
    Francisco J Quintana
    Center for Neurologic Diseases, Brigham and Women s Hospital, Harvard Medical School, 77 Avenue Louis Pasteur, Boston, Massachusetts 02115, USA
    Nature 453:65-71. 2008
    ..Thus, AHR regulates both T(reg) and T(H)17 cell differentiation in a ligand-specific fashion, constituting a unique target for therapeutic immunomodulation...
  44. ncbi Autoimmune inflammation from the Th17 perspective
    Janette Furuzawa-Carballeda
    Department of Immunology and Rheumatology, Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran, Vasco de Quiroga 15 Tlalpan, Mexico City 14000, Mexico
    Autoimmun Rev 6:169-75. 2007
    ..The IL-17/23 axis of inflammation and related molecules may rise as therapeutic targets for treating these and perhaps other autoimmune diseases...
  45. pmc Cytokine-secreting follicular T cells shape the antibody repertoire
    R Lee Reinhardt
    Howard Hughes Medical Institute and Departments of Medicine and Microbiology and Immunology, University of California San Francisco, USA
    Nat Immunol 10:385-93. 2009
    ..Our findings support a model in which B cells compete for cytokines produced by follicular helper T cells that shape the affinity and isotype of the antibody response...
  46. pmc The role of T helper 17 (Th17) and regulatory T cells (Treg) in human organ transplantation and autoimmune disease
    B Afzali
    Department of Nephrology and Transplantation, King s College London, Guy s and St Thomas Hospital, UK
    Clin Exp Immunol 148:32-46. 2007
    ..In this paper we review Th17/IL-17 and Treg biology and expand on this hypothesis...
  47. pmc Simian immunodeficiency virus-induced mucosal interleukin-17 deficiency promotes Salmonella dissemination from the gut
    Manuela Raffatellu
    Department of Medical Microbiology and Immunology, School of Medicine, University of California at Davis, One Shields Avenue, Davis, California 95616 8645, USA
    Nat Med 14:421-8. 2008
    ..We conclude that SIV infection impairs the IL-17 axis, an arm of the mucosal immune response preventing systemic microbial dissemination from the gastrointestinal tract...
  48. pmc Th17 functions as an osteoclastogenic helper T cell subset that links T cell activation and bone destruction
    Kojiro Sato
    Department of Cell Signaling, Graduate School, and COE Program for Frontier Research on Molecular Destruction and Reconstruction of Tooth and Bone, Tokyo Medical and Dental University, Tokyo 113 8549, Japan
    J Exp Med 203:2673-82. 2006
    ..Thus, Th17 is a powerful therapeutic target for the bone destruction associated with T cell activation...
  49. ncbi Cutting edge: An in vivo requirement for STAT3 signaling in TH17 development and TH17-dependent autoimmunity
    Timothy J Harris
    Department of Oncology, Johns Hopkins Sidney Kimmel Comprehensive Cancer Center, Baltimore, MD 21231, USA
    J Immunol 179:4313-7. 2007
    ..Thus, STAT3 is a candidate target for T(H)17-dependent autoimmune disease immunotherapy that could selectively inhibit pathogenic immune pathways...
  50. pmc TGF-beta-induced Foxp3 inhibits T(H)17 cell differentiation by antagonizing RORgammat function
    Liang Zhou
    The Kimmel Center for Biology and Medicine of the Skirball Institute, New York University School of Medicine, New York, New York 10016, USA
    Nature 453:236-40. 2008
    ..Therefore, the decision of antigen-stimulated cells to differentiate into either T(H)17 or T(reg) cells depends on the cytokine-regulated balance of RORgammat and Foxp3...
  51. ncbi T follicular helper cells express a distinctive transcriptional profile, reflecting their role as non-Th1/Th2 effector cells that provide help for B cells
    Tatyana Chtanova
    Garvan Institute of Medical Research, 384 Victoria Street, Darlinghurst, New South Wales 2010, Australia
    J Immunol 173:68-78. 2004
    ..Gene microarrays reveal a highly distinctive transcriptional profile for a third subset of effector T cells that differs markedly from Th1 and Th2 cells...
  52. 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...
  53. pmc Bcl6 and Blimp-1 are reciprocal and antagonistic regulators of T follicular helper cell differentiation
    Robert J Johnston
    Division of Vaccine Discovery, La Jolla Institute for Allergy and Immunology LIAI, 9420 Athena Circle, La Jolla, CA 92037, USA
    Science 325:1006-10. 2009
    ..These findings demonstrate that T(FH) cells are required for proper B cell responses in vivo and that Bcl6 and Blimp-1 play central but opposing roles in T(FH) differentiation...
  54. pmc ICOS-dependent extrafollicular helper T cells elicit IgG production via IL-21 in systemic autoimmunity
    Jared M Odegard
    Department of Immunobiology, Yale School of Medicine, New Haven, CT 06520, USA
    J Exp Med 205:2873-86. 2008
    ....
  55. ncbi Essential role of Stat6 in IL-4 signalling
    K Takeda
    Institute for Molecular and Cellular Biology, Osaka University, Japan
    Nature 380:627-30. 1996
    ..These findings agreed with those obtained in IL-4 deficient mice or using antibodies to IL-4 and the IL-4 receptor. We conclude that Stat6 plays a central role in exerting IL-4 mediated biological responses...
  56. ncbi CNS myeloid DCs presenting endogenous myelin peptides 'preferentially' polarize CD4+ T(H)-17 cells in relapsing EAE
    Samantha L Bailey
    Department of Microbiology Immunology and the Interdepartmental Immunobiology Center, Northwestern University Medical School, Chicago, Illinois 60611, USA
    Nat Immunol 8:172-80. 2007
    ..Our findings indicate a critical function for CNS mDCs in driving relapses in relapsing EAE...
  57. ncbi STAT3 regulates cytokine-mediated generation of inflammatory helper T cells
    Xuexian O Yang
    Department of Immunology, M D Anderson Cancer Center, Houston, Texas 77030, USA
    J Biol Chem 282:9358-63. 2007
    ..Our data thus demonstrate a pathway whereby cytokines regulate THi differentiation through a selective STAT transcription factor that functions to regulate lineage-specific gene expression...
  58. ncbi Role of the novel Th17 cytokine IL-17F in inflammatory bowel disease (IBD): upregulated colonic IL-17F expression in active Crohn's disease and analysis of the IL17F p.His161Arg polymorphism in IBD
    Julia Seiderer
    Department of Medicine II Grosshadern, University of Munich, Germany
    Inflamm Bowel Dis 14:437-45. 2008
    ..His161Arg polymorphism on disease susceptibility and phenotype of Crohn's disease (CD) and ulcerative colitis (UC). In addition, we analyzed the IL17F p.His161Arg polymorphism for potential epistasis with IL23R and NOD2/CARD15 variants...
  59. ncbi Differential T cell costimulatory requirements in CD28-deficient mice
    A Shahinian
    Department of Medical Biophysics and Immunology, University of Toronto, Canada
    Science 261:609-12. 1993
    ..Thus, CD28 is not required for all T cell responses in vivo, suggesting that alternative costimulatory pathways may exist...
  60. ncbi T-cell help for cytotoxic T lymphocytes is mediated by CD40-CD40L interactions
    S P Schoenberger
    Department of Immunohematology and Blood Bank, University Hospital Leiden, The Netherlands
    Nature 393:480-3. 1998
    ..Blockade of CD40L inhibits CTL priming; this inhibition is overcome by signalling through CD40. CD40-CD40L interactions are therefore vital in the delivery of T-cell help for CTL priming...
  61. pmc IL-6 blockade inhibits the induction of myelin antigen-specific Th17 cells and Th1 cells in experimental autoimmune encephalomyelitis
    Satoshi Serada
    Laboratory for Immune Signal, National Institute of Biomedical Innovation, 7 6 8 Saito Asagi, Ibaraki, Osaka 565 0085, Japan
    Proc Natl Acad Sci U S A 105:9041-6. 2008
    ..These findings indicate that anti-IL-6R mAb treatment might represent a novel therapy for human MS...
  62. ncbi Production of interleukin 22 but not interleukin 17 by a subset of human skin-homing memory T cells
    Thomas Duhen
    Institute for Research in Biomedicine, Bellinzona, Switzerland
    Nat Immunol 10:857-63. 2009
    ..Our findings delineate a previously unknown subset of human CD4(+) effector T cells dedicated to skin pathophysiology...
  63. ncbi Follicular B helper T cell activity is confined to CXCR5(hi)ICOS(hi) CD4 T cells and is independent of CD57 expression
    Ata Ur Rasheed
    Department of Tumor Genetics and Immunogenetics, Max Delbrück Center for Molecular Medicine MDC, Berlin, Germany
    Eur J Immunol 36:1892-903. 2006
    ....
  64. pmc IL-17-dependent cellular immunity to collagen type V predisposes to obliterative bronchiolitis in human lung transplants
    William J Burlingham
    Department of Surgery, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin 53792, USA
    J Clin Invest 117:3498-506. 2007
    ..These data suggest that while alloimmunity initiates lung transplant rejection, de novo autoimmunity mediated by col(V)-specific Th17 cells and monocyte/macrophage accessory cells ultimately causes progressive airway obliteration...
  65. ncbi Induction and effector functions of T(H)17 cells
    Estelle Bettelli
    Center for Neurologic Diseases, Brigham and Women s Hospital, Harvard Medical School, Boston, Massachusetts 02115, USA
    Nature 453:1051-7. 2008
    ..In addition, the differentiation factors responsible for their generation have revealed an interesting reciprocal relationship with regulatory T (T(reg)) cells, which prevent tissue inflammation and mediate self-tolerance...
  66. pmc Stage 3 immature human natural killer cells found in secondary lymphoid tissue constitutively and selectively express the TH 17 cytokine interleukin-22
    Tiffany Hughes
    Integrated Biomedical Graduate Program, The Ohio State University College of Medicine, Columbus, Ohio, USA
    Blood 113:4008-10. 2009
    ..In summary, stage 3 iNK cells are highly enriched for IL-22 and IL-26 messenger RNA, and IL-22 protein production, but do not express IL-17A or IL-17F...
  67. pmc Nasal anti-CD3 antibody ameliorates lupus by inducing an IL-10-secreting CD4+ CD25- LAP+ regulatory T cell and is associated with down-regulation of IL-17+ CD4+ ICOS+ CXCR5+ follicular helper T cells
    Henry Yim Wu
    Brigham and Women s Hospital and Harvard Medical School, Boston, MA 02115, USA
    J Immunol 181:6038-50. 2008
    ..Our results demonstrate that nasal anti-CD3 induces CD4(+)CD25(-)LAP(+) regulatory T cells that suppress lupus in mice and that it is associated with down-regulation of T cell help for autoantibody production...
  68. pmc IL-6-dependent and -independent pathways in the development of interleukin 17-producing T helper cells
    Akihiro Kimura
    Laboratory of Immune Regulation, Osaka University Graduate School of Frontier Biosciences, 1 3, Yamada oka, Suita, Osaka, 565 0871, Japan
    Proc Natl Acad Sci U S A 104:12099-104. 2007
    ..In contrast, both Stat1 and Stat3 remained to be activated in naïve T cells cultured with DCCM. These findings represent a different basis for Th17 differentiation from naïve T cells...
  69. pmc Engagement of the type I interferon receptor on dendritic cells inhibits T helper 17 cell development: role of intracellular osteopontin
    Mari L Shinohara
    Department of Cancer Immunology and AIDS, Dana Farber Cancer Institute, 44 Binney Street, Boston, MA 02115, USA
    Immunity 29:68-78. 2008
    ..Definition of the IFNAR-Opn-i axis that controls Th17 development provides insight into regulation of Th cell sublineage development and the molecular basis of type I interferon therapy for MS and other autoimmune diseases...
  70. ncbi Requirement for CD4 T cell help in generating functional CD8 T cell memory
    Devon J Shedlock
    Department of Microbiology, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA
    Science 300:337-9. 2003
    ..These results demonstrate a previously undescribed role for CD4 help in the development of functional CD8 memory...
  71. pmc IL-22-producing "T22" T cells account for upregulated IL-22 in atopic dermatitis despite reduced IL-17-producing TH17 T cells
    Kristine E Nograles
    Laboratory for Investigative Dermatology, The Rockefeller University, New York, NY 10065, USA
    J Allergy Clin Immunol 123:1244-52.e2. 2009
    ..An upregulated TH17/IL-23 pathway was demonstrated in psoriasis. Although potential involvement of TH17 T cells in AD was suggested during acute disease, the role of these cells in chronic AD remains unclear...
  72. pmc CD4+ effector cells default to the Th2 pathway in interferon gamma-deficient mice infected with Leishmania major
    Z E Wang
    Department of Medicine, University of California San Francisco 94143
    J Exp Med 179:1367-71. 1994
    ..These data suggest that CD4+ T cells that normally respond to antigens by differentiation to Th1 cells default to the Th2 pathway in the absence of endogenous IFN-gamma...
  73. ncbi The proinflammatory effect of prostaglandin E2 in experimental inflammatory bowel disease is mediated through the IL-23-->IL-17 axis
    Amir F Sheibanie
    Department of Physiology, Temple University School of Medicine, 3420 North Broad Street, Philadelphia, PA 19140, USA
    J Immunol 178:8138-47. 2007
    ..These studies suggest that high levels of PGE(2) exacerbate the inflammatory process through the preferential expression and release of DC-derived IL-23 and the subsequent support of the autoreactive/inflammatory Th17 phenotype...
  74. ncbi TH17 cells contribute to uveitis and scleritis and are expanded by IL-2 and inhibited by IL-27/STAT1
    Ahjoku Amadi-Obi
    Molecular Immunology Section, National Eye Institute, National Institutes of Health, Bethesda, Maryland 20892, USA
    Nat Med 13:711-8. 2007
    ....
  75. ncbi ICOS is essential for effective T-helper-cell responses
    A Tafuri
    Amgen Institute, 620 University Avenue, Toronto, Ontario M5G 2C1, Canada
    Nature 409:105-9. 2001
    ..ICOS-deficient T cells primed in in vivo and restimulated in vitro with specific antigen produce only low levels of interleukin-4, but remain fully competent to produce interferon-gamma...
  76. ncbi A fundamental role for interleukin-21 in the generation of T follicular helper cells
    Alexis Vogelzang
    Department of Immunology, Garvan Institute of Medical Research, 384 Victoria Street, Darlinghurst, NSW 2010, Australia
    Immunity 29:127-37. 2008
    ..This study reveals a previously unappreciated role for Tfh cells in the formation of the GC and isotype switching through a CD4(+) T cell-intrinsic requirement for IL-21...
  77. ncbi CCR4 versus CCR10 in human cutaneous TH lymphocyte trafficking
    Dulce Soler
    Millennium Pharmaceuticals, Inflammation Department, Cambridge, MA 02115, USA
    Blood 101:1677-82. 2003
    ..Thus, CCR10 is unlikely to be necessary for cutaneous homing of TH cells in the models studied here. CCR10 may instead play a role in the movement of specialized "effector" cutaneous TH cells to and/or within epidermal microenvironments...
  78. ncbi Diversification of T-helper-cell lineages: finding the family root of IL-17-producing cells
    Chen Dong
    Department of Immunology, MD Anderson Cancer Center, Houston, Texas 77030, USA
    Nat Rev Immunol 6:329-33. 2006
    ....
  79. ncbi TGF-beta and IL-6 drive the production of IL-17 and IL-10 by T cells and restrain T(H)-17 cell-mediated pathology
    Mandy J McGeachy
    Schering Plough Biopharma, Palo Alto, California 94304, USA
    Nat Immunol 8:1390-7. 2007
    ..Our findings suggest that full acquisition of pathogenic function by effector T(H)-17 cells is mediated by IL-23 rather than by TGF-beta and IL-6...
  80. ncbi A RING-type ubiquitin ligase family member required to repress follicular helper T cells and autoimmunity
    Carola G Vinuesa
    Division of Immunology and Genetics, John Curtin School of Medical Research, The Australian National University, Canberra, ACT 2601, Australia
    Nature 435:452-8. 2005
    ..The Roquin protein is distinguished by the presence of a CCCH zinc-finger found in RNA-binding proteins, and localization to cytosolic RNA granules implicated in regulating messenger RNA translation and stability...
  81. 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
    ....
  82. ncbi Broad repertoire of the CD4+ Th cell response in spontaneously controlled hepatitis C virus infection includes dominant and highly promiscuous epitopes
    Julian Schulze zur Wiesch
    Partners AIDS Research Center and Infectious Disease Division, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02129, USA
    J Immunol 175:3603-13. 2005
    ..This comprehensive characterization of CD4(+) T cell epitopes in resolved HCV infection provides important information to facilitate studies of immunopathogenesis and HCV vaccine design and evaluation...
  83. ncbi Interleukin 17-producing T helper cells and interleukin 17 orchestrate autoreactive germinal center development in autoimmune BXD2 mice
    Hui Chen Hsu
    Department of Medicine, University of Alabama at Birmingham, Birmingham, Alabama 35294, USA
    Nat Immunol 9:166-75. 2008
    ..These findings suggest a mechanism by which IL-17 drives autoimmune responses by promoting the formation of spontaneous GCs...
  84. ncbi The role of CD4(+) T helper cells in the cytotoxic T lymphocyte response to HIV-1
    M Altfeld
    Partners AIDS Research Center, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA 02114, USA
    Curr Opin Immunol 12:375-80. 2000
    ....
  85. ncbi The nuclear orphan receptor NR2F6 suppresses lymphocyte activation and T helper 17-dependent autoimmunity
    Natascha Hermann-Kleiter
    Department for Medical Genetics, Molecular and Clinical Pharmacology, Medical University Innsbruck, 6020 Innsbruck, Austria
    Immunity 29:205-16. 2008
    ..Our study establishes NR2F6 as a transcriptional repressor of IL-17 expression in Th17-differentiated CD4(+) T cells in vitro and in vivo...
  86. pmc The interleukin 23 receptor is essential for the terminal differentiation of interleukin 17-producing effector T helper cells in vivo
    Mandy J McGeachy
    Schering Plough Biopharma, Palo Alto, California 94304, USA
    Nat Immunol 10:314-24. 2009
    ..These defects were associated with less proliferation; consequently, fewer effector T(H)-17 cells were produced in the lymph nodes and hence available to emigrate to the bloodstream and tissues...
  87. ncbi Understanding the IL-23-IL-17 immune pathway
    Brent S McKenzie
    Discovery Research, DNAX Research Inc, 901 California Ave, Palo Alto, CA 94304 1104, USA
    Trends Immunol 27:17-23. 2006
    ..By comparing the pathophysiological function of IL-12 and IL-23 in the context of host defense and autoimmune inflammation, we are beginning to understand the novel IL-23-IL-17 immune pathway...
  88. ncbi Identification of a human helper T cell population that has abundant production of interleukin 22 and is distinct from T(H)-17, T(H)1 and T(H)2 cells
    Sara Trifari
    Department of Immunology, Genentech, South San Francisco, California, USA
    Nat Immunol 10:864-71. 2009
    ..AHR agonists substantially altered the balance of IL-22- versus IL-17-producing cells. This subset of IL-22-producing cells may be important in skin homeostasis and pathology...
  89. pmc Human type 1 and 17 responses in latent tuberculosis are modulated by coincident filarial infection through cytotoxic T lymphocyte antigen-4 and programmed death-1
    Subash Babu
    National Institutes of Health International Center for Excellence in Research, India
    J Infect Dis 200:288-98. 2009
    ....
  90. ncbi Novel signal transducer and activator of transcription 3 (STAT3) mutations, reduced T(H)17 cell numbers, and variably defective STAT3 phosphorylation in hyper-IgE syndrome
    Ellen D Renner
    Department of Pediatrics, University of Washington School of Medicine and Children s Hospital and Regional Medical Center, Seattle, Wash 98101 1304, USA
    J Allergy Clin Immunol 122:181-7. 2008
    ..Recently it was shown that heterozygous signal transducer and activator of transcription 3 (STAT3) mutations cause autosomal-dominant HIES...
  91. pmc Human Th17 cells
    Sergio Romagnani
    Department of Internal Medicine, University of Florence, Viale Morgagni, 85 Firenze 50134, Italy
    Arthritis Res Ther 10:206. 2008
    ..In contrast, it is unlikely that Th17 cells contribute to the pathogenesis of human allergic IgE-mediated disorders, because IL-4 and IL-25 (a powerful inducer of IL-4) are both potent inhibitors of Th17 cell development...
  92. ncbi Hyperproduction of IL-23 and IL-17 in patients with systemic lupus erythematosus: implications for Th17-mediated inflammation in auto-immunity
    Chun Kwok Wong
    Department of Chemical Pathology, The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, Hong Kong
    Clin Immunol 127:385-93. 2008
    ..05). Ex vivo inductions of IL-17 by IL-23 or IL-18 from co-stimulated lymphocytes were significantly higher in SLE patients than controls (all p<0.05). The activated IL-23/IL-17 axis is important for the inflammatory immunity in SLE...
  93. ncbi Suppressors of cytokine signaling proteins are differentially expressed in Th1 and Th2 cells: implications for Th cell lineage commitment and maintenance
    Charles E Egwuagu
    Laboratory of Immunology, National Eye Institute, National Institutes of Health, Bethesda, MD 20892, USA
    J Immunol 168:3181-7. 2002
    ....
  94. ncbi Role of CXCR5 and CCR7 in follicular Th cell positioning and appearance of a programmed cell death gene-1high germinal center-associated subpopulation
    Nicole M Haynes
    Howard Hughes Medical Institute, University of California, San Francisco, CA 94143, USA
    J Immunol 179:5099-108. 2007
    ....
  95. pmc Differential regulation of central nervous system autoimmunity by T(H)1 and T(H)17 cells
    Ingunn M Stromnes
    Department of Immunology, Box 357650, HSC H474B, 1959 NE Pacific Street, Seattle, Washington 98195, USA
    Nat Med 14:337-42. 2008
    ..In contrast, T cells showing a wide range of T(H)17:T(H)1 ratios induce spinal cord parenchymal inflammation. These findings reveal critical differences in the regulation of inflammation in the brain and spinal cord...
  96. ncbi The link between IL-23 and Th17 cell-mediated immune pathologies
    Mandy J McGeachy
    Schering Plough Biopharma Formerly DNAX Research, 901 California Avenue, Palo Alto, CA 94304, United States
    Semin Immunol 19:372-6. 2007
    ..Finally, the roles of IL-23 in inflammatory diseases in relation to Th17 function will be discussed...
  97. ncbi Functional yet balanced reactivity to Candida albicans requires TRIF, MyD88, and IDO-dependent inhibition of Rorc
    Antonella De Luca
    Department of Experimental Medicine and Biochemical Sciences, University of Perugia, Perugia, Italy
    J Immunol 179:5999-6008. 2007
    ..This is the first study to show that the same tryptophan catabolites can foster dendritic cell-supported generation of Foxp3(+) cells and mediate, at the same time, inhibition of RORgammat-expressing T cells...
  98. ncbi Th17 T cells: linking innate and adaptive immunity
    Brigitta Stockinger
    Division of Molecular Immunology, The MRC National Institute for Medical Research, Mill Hill, London NW7 1AA, UK
    Semin Immunol 19:353-61. 2007
    ..In order to avoid too many repetitions we focus this review mainly on publications in 2006 and 2007 and refer to a number of reviews, which cover earlier aspects of Th17/IL-17 biology...
  99. ncbi Chronically inflamed human tissues are infiltrated by highly differentiated Th17 lymphocytes
    Jerome Pene
    Institut National de la Sante et de la Recherche Medicale, Unité 844, Montpellier, France
    J Immunol 180:7423-30. 2008
    ....
  100. pmc The type I IFN induction pathway constrains Th17-mediated autoimmune inflammation in mice
    Beichu Guo
    Department of Microbiology, Immunology, and Molecular Genetics, 8 240 Factor Building, University of California, 10833 Le Conte Avenue, Los Angeles, California 90095, USA
    J Clin Invest 118:1680-90. 2008
    ....
  101. ncbi A brief history of T(H)17, the first major revision in the T(H)1/T(H)2 hypothesis of T cell-mediated tissue damage
    Lawrence Steinman
    Interdepartmental Program in Immunology, Department of Neurology and Neurological Sciences, Beckman Center for Molecular Medicine, Stanford University, Stanford, California 94305, USA
    Nat Med 13:139-45. 2007
    ..The evolution of our understanding of the T(H)17 pathway illuminates a shift in immunologists' perspectives regarding the basis of tissue damage, where for over 20 years the role of T(H)1 cells was considered paramount...

Research Grants67

  1. Bi-functional Therapeutics for Allergy-BFTA
    Swey Shen Chen; Fiscal Year: 2010
    ..PUBLIC HEALTH RELEVANCE: The Project of bi-functional pan-IgE therapeutics may yield a commercializable product for treating IgE-mediated allergic diseases of different indications. ..
  2. Mechanisms of adaptive immunity to P. aeruginosa in the lung
    Gregory P Priebe; Fiscal Year: 2013
    ..Knowledge gained from these studies will support the development of better vaccines for pneumonia as well as an improved understanding of how to prevent lung infections in patients with cystic fibrosis. ..
  3. Gold Nanoparticle Assisted Delivery of Cancer Vaccines and Immune Stimulants
    Adam Lin; Fiscal Year: 2013
    ..This design would dramatically lower the cost of immunotherapy compared cellular vaccines. They are easily synthesized, versatile and can potentially target later stage cancers by using inducing anti-tumor immunity over the whole body. ..
  4. Novel Therapeutic Vaccines for Chronic HBV
    ROBERT GERALD WHALEN; Fiscal Year: 2013
    ..Success in developing this innovative DNA-based therapeutic vaccine for chronic HBV infection would fill a considerable unmet need in the treatment of this disease, which represents a major public health burden. ..
  5. Analyzing the Efficacy of Galectin-1 Ligand Inhibition in Adoptive T cell Therapy
    JENNA GEDDES SWEENEY; Fiscal Year: 2012
    ....
  6. Imaging and Function of the Immunological Synapse
    David C Parker; Fiscal Year: 2012
    ....
  7. SPORE in Lymphoma
    Richard Ambinder; Fiscal Year: 2009
    ..abstract_text> ..
  8. Synthesis of immunogenic glycolipopeptides for the development of vaccines for Ch
    Katja Michael; Fiscal Year: 2010
    ..The results of this research could lead to a vaccine which would have a tremendous impact on public health, not only by saving thousands of lives in Central America, but also by protecting individuals under risk in the U.S. ..
  9. Regulation of miRNA expression during helper T cell differentiation
    KARL MARK ANSEL; Fiscal Year: 2010
    ..These studies may lead to novel approaches for vaccine development, or for designing therapies for asthma and other allergic diseases, autoimmune diseases, and chronic inflammation. ..
  10. Flexibility and Commitment in Post-Effector Cd4 Lymphocytes
    Mark R Boothby; Fiscal Year: 2013
    ....
  11. control of Inflammation by regulatory T cells and BCL6
    Alexander L Dent; Fiscal Year: 2012
    ..This work will offer new insights into the molecular regulation of regulatory T cells, thus facilitating the development of new therapies targeting BCL6 for treatment of inflammation and autoimmunity. ) ..
  12. Manipulation of Follicular Helper T Cells in Immunity and Autoimmunity
    Joseph Craft; Fiscal Year: 2013
    ....
  13. Molecular Mechanisms of IL-4 and IL-13 Signaling
    Achsah D Keegan; Fiscal Year: 2010
    ..Our studies will provide a greater understanding of their mechanism of action and contribution to allergic inflammation. This new knowledge could help to develop better approaches to treat allergy and asthma. ..
  14. Regulation of MHC Class II Genes
    Jeremy M Boss; Fiscal Year: 2013
    ..Understanding the molecular bases for how these genes are regulated will serve to predict targets and pathways that could be manipulated in clinical settings to treat the above diseases. ..
  15. Defining modes of helper T cell motility within inflamed tissues
    Michael Glen Overstreet; Fiscal Year: 2012
    ....
  16. Identification and functional characterization of a novel positive cis-control el
    SOPHIA DORCHEVA SARAFOVA; Fiscal Year: 2013
    ....
  17. Anti-PV1 Therapy for Pancreatic Cancer
    RADU VIRGIL STAN; Fiscal Year: 2013
    ..In summary, the data we expect to obtain are relevant to the pathophysiology of cancer, establishing PV1 as a novel target for cancer treatment, which is one of NCI's stated goals. ..
  18. Overcoming established anaphylactic hypersensitivity to peanuts
    Kelvin P Lee; Fiscal Year: 2013
    ..The Specific Aims are: 1). Define the role of CD28 in generating and maintaining PN-specific immune responses involved in PN anaphylaxis, 2). Determine if blocking CD28 activation overcomes established PN hypersensitivity. ..
  19. INTESTINAL REGULATION OF ThPOK EXPRESSION AND CD4 HELPER T CELL FUNCTION
    DANIEL S MUCIDA; Fiscal Year: 2013
    ....
  20. B LYMPHOCYTE MIGRATION AND HOMEOSTASIS
    Jason G Cyster; Fiscal Year: 2013
    ..The research will also begin to unravel how this ligand-receptor system affects inflammatory gene expression during chronic tissue inflammation. ..
  21. In vivo imaging of T and B cell interactions in germinal center initiation
    Ann M Haberman; Fiscal Year: 2012
    ..The proposed experiments will be an important step forward for future studies in germinal center development as well as vaccine design. ..
  22. MELANOMA VACCINE FOR HELPER T CELLS COMBINED WITH TARGETED OR IMMUNE THERAPIES
    CRAIG LEE SLINGLUFF; Fiscal Year: 2013
    ....
  23. B7H1 Mediated Immunosuppression in Glioma
    Andrew T Parsa; Fiscal Year: 2013
    ..The availability of drugs that inhibit the PI(3)K pathway or block B7-H1 and its receptor PD-1 provides a natural extension of these studies into the realm of patient care. ..
  24. Modulation of Microglia and T Cell Interactions in Malignant Glioma
    AMY BETH HEIMBERGER; Fiscal Year: 2013
    ..By further delineating the mechanisms underlying the failure of the immune system to eradicate or suppress gliomas, we hope to improve the efficacy of future immunotherapy, increase longevity and quality of life of glioma patients. ..
  25. Dendritic Cell Control of Skin Immunity
    Terri M Laufer; Fiscal Year: 2013
    ....
  26. TCR Engineered CD4 Cells as Helpers in Tumor Immunity
    Bijay Mukherji; Fiscal Year: 2012
    ....
  27. Protective CD4+ T cells
    MARC KEVIN JENKINS; Fiscal Year: 2013
    ..Accomplishing our specific aims with a robust defined in vivo model system could guide vaccine development against this recalcitrant class of pathogens. ..
  28. Mechanisms of highly efficient HIV transfer at virological synapses
    Benjamin Chen; Fiscal Year: 2012
    ..A better understanding of VS-mediated viral spread, will allow us to devise novel strategies to inhibit HIV spread with new drugs, microbicides or vaccines. ..
  29. Role of IDO in Malignancy
    David H Munn; Fiscal Year: 2013
    ....
  30. Epitope-driven deimmunization of Factor VIII
    ANNE SEARLS DE GROOT; Fiscal Year: 2010
    ..The proposed reengineered protein will be evaluated in a mice that have a hemophilia as well as in mice that have a human- like immune system. ..
  31. Signaling and Cell Biology of TIM-1
    Lawrence P Kane; Fiscal Year: 2013
    ..We believe that the studies outlined in this proposal have great potential to aid in the understanding of the effects of in vivo modulation of TIM-1, which has shown potential in pre-clinical models of asthma. ..
  32. B7-H1 mediated immunosuppression in immunocompetent animal model of gliomas
    AARON JOHN CLARK; Fiscal Year: 2013
    ..We will determine if B7-H1 expression by GL261 tumor cells induces local immunoresistance that affects tumor growth, immunologic tumor microenvironment, and response to vaccine therapy. ..
  33. Mechanisms generating suppressor CD4 T cells by thymocyte-mediated development
    Cheong Hee Chang; Fiscal Year: 2012
    ..The outcome of the proposed research will provide new insights into how T-CD4 T cells modulate immunity and will facilitate the clinical translation of T-CD4 T cell mediated immunotherapy in the future. ..
  34. Enhancing CD8 T Cell Function by Abrogating Inhibition by Regulatory Proteins
    Joseph N Blattman; Fiscal Year: 2010
    ....
  35. Influence of Naive Lymphocyte Repertoire Size on Vaccination Efficancy
    MARC KEVIN JENKINS; Fiscal Year: 2010
    ..Therefore, these studies have the potential to predict who will not respond to this important vaccine and suggest a solution to this problem. ..
  36. Leukocyte subset identification by single cell analysis of BTB-ZF gene
    DEREK B SANT'ANGELO; Fiscal Year: 2013
    ..Finally, since this family of transcription factors is highly conserved in humans, our studies have the potential to lead to new diagnostic tests and/or therapies. ..
  37. MYC-induced breach of B-cell anergy in AIDS-related NHLs
    Yosef Refaeli; Fiscal Year: 2010
    ..In addition, the details surrounding the mechanisms by which MYC affects lymphoid tolerance and homeostasis may provide further insights into the role of MYC in lymphoid neoplasia. ..
  38. Glucocorticoid receptor translational isoforms in asthma
    Nick Lu; Fiscal Year: 2013
    ..In addition, these studies may provide a basis for the development of anti- inflammatory drugs targeting or altering the expression of selective GR isoforms. ..
  39. Cellular dynamics in germinal centers during vaccination
    Michel C Nussenzweig; Fiscal Year: 2013
    ..The proposed studies will provide new insights into mechanisms operating in germinal centers including somatic mutation that are essential to developing novel vaccination strategies to overcome barriers to host protection. ..
  40. Immune Mechanisms of Alloinjury
    John A Belperio; Fiscal Year: 2013
    ..Discoveries generated by this proposal will be the basis for future therapeutic trials of pharmaceutical agents that inhibit CCR4/ligands interaction with the goal of preventing/treating BOS post-lung transplantation. ..
  41. Role of PTPRkappa in Lck Regulation During T cell Development
    JANE CHERIE YACIUK; Fiscal Year: 2010
    ....
  42. Role of miRNAs in Th2-Driven inflammation in Asthma
    KARL MARK ANSEL; Fiscal Year: 2013
    ..These studies will focus first on 3 strong candidate miRNAs identified in preliminary functional screens and expression profiling. ..
  43. Role of BCL11B in CD4+ T Cells
    Dorina Avram; Fiscal Year: 2013
    ....
  44. HELPER T CELL REGULATION IN MURINE LEISHMANIASIS
    Steven L Reiner; Fiscal Year: 2012
    ....
  45. IMMUNOLOGIC MECHANISMS THAT PREVENT AUTOIMMUNITY
    Harvey Cantor; Fiscal Year: 2013
    ....
  46. Functional analyses of antiviral CD4+ T cell responses
    J Lindsay Whitton; Fiscal Year: 2013
    ..Might IFN[unreadable] be the "link" by which CD4+ T cells help the development of CD8+ T cell memory? Is the role of IFN[unreadable] the same for specific &non-specific CD4+ helper T cells? ..
  47. Host and Bacterial Factors in Disease due to H. pylori
    Kathryn A Eaton; Fiscal Year: 2010
    ..This will allow us to hire additional staff to ensure rapid completion of the remaining experiments. With these changes we fully expect to complete these experiments in 2 years. ..
  48. The Relationship between TCR Revision and Follicular Helper T Cells
    Pamela J Fink; Fiscal Year: 2013
    ..These experiments will help place TCR revision within the larger framework of T cell immunology, and will explore how TCR revision may impact the B cell arm of the adaptive immune response. ..
  49. Dengue Epitope Vaccine,Tetravalent & MHCII-Targeted
    J Thomas August; Fiscal Year: 2007
    ..abstract_text> ..
  50. The effects of follicular helper T cells on germinal center B cells.
    HEIDI ANN SCHREIBER; Fiscal Year: 2013
    ..The proposed studies here will determine whether T cells, through their interactions with GC B cells, are essential in regulating the emergence of self-reactive antibodies. ..
  51. Exploring the action of IL-27 in EAE through models of attenuated disease
    MELISSA LISE CULLIMORE; Fiscal Year: 2011
    ..PUBLIC HEALTH RELEVANCE: This project investigates animal models of multiple sclerosis where the animals do not get sick. This research will hopefully lead to a better understanding of how to treat multiple sclerosis in humans. ..
  52. Role of BAFF in regulation of B cell peripheral tolerance
    Neda Nikbakht; Fiscal Year: 2012
    ....
  53. Autoantibody production and regulatory T cells
    Stephen B Gauld; Fiscal Year: 2012
    ..These studies will help define a novel mechanism by which anergic B cells are regulated, with potential for developing new therapeutic strategies for the treatment of autoimmunity. ..
  54. REGULATION OF AUTOREACTIVE T CELLS IN IL10 KNOCKOUT MICE
    Peter Ernst; Fiscal Year: 1999
    ..Clarifying the role of these cytokines controlling auto-reactive T cells will define the pathogenesis of colitis and identify therapeutic strategies that can be applied to these intestinal diseases. ..
  55. Immunodeficiency and Autoimmunity
    ABUL ABBAS; Fiscal Year: 2009
    ..This project will provide valuable information about why immune deficiencies are associated with autoimmunity, and may give insights into the general mechanisms of failure of tolerance and development of systemic autoimmunity. ..
  56. IMMUNE MEDIATED BLADDER INFLAMMATION
    Timothy Ratliff; Fiscal Year: 2002
    ..10 T cell receptor transgenic model, and (3) determine the effects of CD4+ T cell-directed chronic bladder inflammation on bladder function and evaluate strategies for modifying the response. ..
  57. MEMBRANE RECEPTOR TRAFFICKING AND ANTIGEN PROCESSING
    Richard Mitchell; Fiscal Year: 1999
    ....
  58. MULTI-EPITOPE MELANOMA VACCINES FOR CD4 AND CD8 T-CELLS
    Craig Slingluff; Fiscal Year: 2009
    ....
  59. HUMAN IMMUNODEFICIENCY VIRUS AND HEMATOPOIESIS
    Colin Sieff; Fiscal Year: 1993
    ....
  60. Cellular Immunity Against Ehrlichia chaffeensis
    ROMAN GANTA; Fiscal Year: 2007
    ..chaffeensis and other closely related organisms. ..
  61. EXPRESSION & FUNCTION OF HLA ANTIGEN ON CARDIAC MYOCYTES
    Aftab Ansari; Fiscal Year: 1990
    ....
  62. Importance of CD5 for the function of regulatory T cells
    Subbarao Bondada; Fiscal Year: 2009
    ..Here we plan to demonstrate that in an in vivo animal model of colitis induced by disease causing T cells, the function of T-Regs is regulated by CD5 expression. ..
  63. GROWTH FACTOR-DEPENDENT NORMAL & LEUKEMIC CELL GROWTH
    Daniela Santoli; Fiscal Year: 1992
    ....
  64. MECHANISM OF CYCLOPHOSPHAMIDE-INDUCED IMMUNOENHANCEMENT
    Thomas Kawabata; Fiscal Year: 1990
    ....
  65. GP120-MEDIATED UNCOUPLING OF T CELL RECEPTOR
    Frederick Goldman; Fiscal Year: 1993
    ..Additionally, immunoprecepitation of various kinases will be carried out and their activity and specificity will be assessed using both in vivo and in vitro assays...
  66. MECHANISMS TO ENHANCE CYTOLYTIC T CELL RESPONSES TO HIV
    J August; Fiscal Year: 1999
    ..Finally, the appropriate formulation will be tested for the co-delivery with gag DNA of cytokines, especially IL-2, IL-12, gamma-INF and GMCSF, in the augmentation of the cytolytic response. ..
  67. Cellular Immunity Against Ehrlichia chaffeensis
    ROMAN GANTA; Fiscal Year: 2002
    ..chaffeensis and other closely related organisms. ..