Genomes and Genes
Gene Symbol: Rag1
Description: recombination activating gene 1
Alias: Rag-1, V(D)J recombination-activating protein 1, recombinase activating gene 1, recombination activating protein 1
Publications200 found, 100 shown here
- The quantitative assessment of MHC II on thymic epithelium: implications in cortical thymocyte developmentSoo Jung Yang
Laboratory of Cellular and Molecular Immunology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA
Int Immunol 18:729-39. 2006..We discuss possible mechanisms for positive selection by weak interactions in the presence of such preformed MHC II aggregate units in cTEC...
- Innate and adaptive interleukin-22 protects mice from inflammatory bowel diseaseLauren A Zenewicz
Department of Immunobiology, Yale University School of Medicine, New Haven, CT 06520 USA
Immunity 29:947-57. 2008..In addition, IL-22 expression was differentially regulated between NK cell subsets. Thus, both the innate and adaptive immune responses have developed protective mechanisms to counteract the damaging effects of inflammation on tissues...
- RAG-1 and RAG-2, adjacent genes that synergistically activate V(D)J recombinationM A Oettinger
Whitehead Institute for Biomedical Research, Cambridge, MA 02142
Science 248:1517-23. 1990..RAG-1 and RAG-2 might activate the expression of the V(D)J recombinase but, more likely, they directly participate in the recombination reaction...
- Adaptive Foxp3+ regulatory T cell-dependent and -independent control of allergic inflammationMaria A Curotto de Lafaille
Program of Molecular Pathogenesis, The Kimmel Center for Biology and Medicine of the Skirball Institute, New York University School of Medicine, New York, NY 10016, USA
Immunity 29:114-26. 2008..Thus, whereas adaptive Foxp3(+) Treg cells regulate sensitization to allergens and the severity of chronic inflammation, IFN-gamma-producing cells can play a beneficial role in inflammatory conditions involving eosinophils...
- Enteric flora expands gut lamina propria CX3CR1+ dendritic cells supporting inflammatory immune responses under normal and inflammatory conditionsJan Hendrik Niess
Department of Internal Medicine I, Ulm University, Ulm, Germany
J Immunol 184:2026-37. 2010..The local bacteria-driven accumulation of CX(3)CR1(+) DCs seems to support inflammatory immune responses...
- Different B cell populations mediate early and late memory during an endogenous immune responseKathryn A Pape
Department of Microbiology, Center for Immunology, University of Minnesota Medical School, Minneapolis, MN 55455, USA
Science 331:1203-7. 2011..Thus, we propose that memory relies on swIg(+) cells until they disappear and serum immunoglobulin falls to a low level, in which case memory resides with durable IgM(+) reserves...
- Interleukin 7 signaling in dendritic cells regulates the homeostatic proliferation and niche size of CD4+ T cellsMartin Guimond
Pediatric Oncology Branch, National Cancer Institute, National Institute of Diabetes, Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA
Nat Immunol 10:149-57. 2009..Our results indicate that IL-7Ralpha(+) DCs are regulators of the peripheral CD4(+) T cell niche and that IL-7 signals in DCs prevent uncontrolled CD4(+) T cell population expansion in vivo...
- AID and RAG1 do not contribute to lymphomagenesis in Emu c-myc transgenic miceR M Nepal
Department of Immunology, University of Toronto, Medical Sciences Building, Toronto, Canada
Oncogene 27:4752-6. 2008DNA breaks caused by recombination-activating gene 1 (RAG1) and activation-induced cytidine deaminase (AID) induce c-myc/immunoglobulin (Ig) heavy chain chromosomal translocations and thereby stimulate lymphomagenesis...
- Regulation of hierarchical clustering and activation of innate immune cells by dendritic cellsSuk Jo Kang
Howard Hughes Medical Institute, Department of Medicine, University of California, San Francisco, San Francisco, CA 94143 0795, USA
Immunity 29:819-33. 2008..Thus, spatial organization of the immune response by DCs between 6 and 24 hr ensures functional activation of innate cells, which restricts pathogens before adaptive immunity is fully activated...
- No requirement for V(D)J recombination in p53-deficient thymic lymphomaM J Liao
Department of Biochemistry and Biophysics, University of North Carolina at Chapel Hill Medical School, Chapel Hill, North Carolina 27599, USA
Mol Cell Biol 18:3495-501. 1998....
- The BCL2A1 gene as a pre-T cell receptor-induced regulator of thymocyte survivalMalay Mandal
Department of Medicine, Section of Rheumatology, University of Chicago, Chicago, IL 60637, USA
J Exp Med 201:603-14. 2005..Finally, we suggest that pre-TCR-induced A1 overexpression can contribute to T cell leukemia in both mice and humans...
- Autoreactive B cell responses to RNA-related antigens due to TLR7 gene duplicationPrapaporn Pisitkun
Laboratory of Immunogenetics, National Institute of Allergy and Infectious Diseases NIAID, NIH, Rockville, MD 20852, USA
Science 312:1669-72. 2006..These results reveal high divergence in mouse Y chromosomes and represent a good example of gene copy number qualitatively altering a polygenic disease manifestation...
- 53BP1 facilitates long-range DNA end-joining during V(D)J recombinationSimone Difilippantonio
Experimental Immunology Branch, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892 1360, USA
Nature 456:529-33. 2008..These data suggest a more general role for 53BP1 in maintaining genomic stability during long-range joining of DNA breaks...
- Mechanisms of tolerance induction in major histocompatibility complex class II-restricted T cells specific for a blood-borne self-antigenT Zal
Department of Molecular Immunology, National Institute for Medical Research, Mill Hill, London, United Kingdom
J Exp Med 180:2089-99. 1994..When crossed onto a Rag1-/- background to prevent endogenous T cell receptor rearrangements, these peripheral potentially autoreactive cells ..
- The recombination activating gene-1 (RAG-1) transcript is present in the murine central nervous systemJ J Chun
Whitehead Institute for Biomedical Research, Cambridge, Massachusetts 02142
Cell 64:189-200. 1991..The results suggest that RAG-1 functions in neurons, where its role might be to recombine elements of the neuronal genome site-specifically, or to prevent detrimental alterations of the genome in these long-lived cells...
- Identification of two catalytic residues in RAG1 that define a single active site within the RAG1/RAG2 protein complexS D Fugmann
Howard Hughes Medical Institute, Section of Immunobiology, Yale University School of Medicine, New Haven, Connecticut 06520, USA
Mol Cell 5:97-107. 2000During V(D)J recombination, the RAG1 and RAG2 proteins cooperate to catalyze a series of DNA bond breakage and strand transfer reactions...
- Transcriptional repressor BCL6 controls Th17 responses by controlling gene expression in both T cells and macrophagesArpita Mondal
Department of Microbiology and Immunology, Indiana University School of Medicine, Indianapolis, IN 46202, USA
J Immunol 184:4123-32. 2010..BCL6-deficient T cells transplanted into Rag1(-/-) mice produced wild-type levels of IL-17, indicating that, in vivo, BCL6-deficient T cells develop relatively ..
- NLRP10 is a NOD-like receptor essential to initiate adaptive immunity by dendritic cellsStephanie C Eisenbarth
Department of Laboratory Medicine, Yale University School of Medicine, New Haven, Connecticut 06520, USA
Nature 484:510-3. 2012....
- Onset of TCR-beta gene rearrangement and role of TCR-beta expression during CD3-CD4-CD8- thymocyte differentiationD I Godfrey
DNAX Research Institute, Palo Alto, CA 94304
J Immunol 152:4783-92. 1994....
- B lymphocytes induce the formation of follicular dendritic cell clusters in a lymphotoxin alpha-dependent fashionY X Fu
Department of Laboratory Medicine Pathology, Washington University School of Medicine, St Louis, Missouri 63110, USA
J Exp Med 187:1009-18. 1998..Thus, B cells themselves provide an essential signal that induces and maintains the lymphoid microenvironment essential for GC formation and class-switched Ig responses...
- Myelin oligodendrocyte glycoprotein-specific T cell receptor transgenic mice develop spontaneous autoimmune optic neuritisEstelle Bettelli
Center for Neurologic Diseases, Brigham and Women s Hospital and Harvard Medical School, Boston, MA 02115, USA
J Exp Med 197:1073-81. 2003..These results demonstrate that clinical manifestations of CNS autoimmune disease will vary depending on the identity of the target autoantigen and that MOG-specific T cell responses are involved in the genesis of isolated optic neuritis...
- Topical vitamin D3 and low-calcemic analogs induce thymic stromal lymphopoietin in mouse keratinocytes and trigger an atopic dermatitisMei Li
Institut de Génétique et de Biologie Moléculaire et Cellulaire and Institut Clinique de la Souris, BP10142, 67404 Illkirch Cedex, France
Proc Natl Acad Sci U S A 103:11736-41. 2006..We propose molecular mechanisms through which vitamin D3 and retinoic acid signalings could be involved in the pathogenesis of atopic diseases...
- The V(D)J recombination activating gene, RAG-1D G Schatz
Whitehead Institute for Biomedical Research, Nine Cambridge Center, Massachusetts 02142
Cell 59:1035-48. 1989..RAG-1 may activate V(D)J recombination indirectly, or it may encode the V(D)J recombinase itself...
- Swift entry of myelin-specific T lymphocytes into the central nervous system in spontaneous autoimmune encephalomyelitisGlaucia C Furtado
Molecular Pathogenesis Program, Kimmel Center for Biology and Medicine of the Skirball Institute, New York University School of Medicine, New York, NY 10016, USA
J Immunol 181:4648-55. 2008..Taken together, our results suggest that peripheral activation of T cells in draining lymph nodes is an early event in the development of EAE, which paves the way for the initial burst of IFN-gamma-producing CD4(+) T cell into the CNS...
- Mutations in T-cell antigen receptor genes alpha and beta block thymocyte development at different stagesP Mombaerts
Howard Hughes Medical Institute, Center for Cancer Research, Cambridge, Massachusetts
Nature 360:225-31. 1992..TCR-alpha is irrelevant in these developmental processes. The development of gamma delta T cells does not depend on either TCR-alpha or TCR-beta...
- Novel role of the Ras cascade in memory B cell responseYoshimasa Takahashi
Department of Immunology, National Institute of Infectious Diseases, Shinjuku, Tokyo, Japan
Immunity 23:127-38. 2005..Thus, our data suggest that upon antigen stimulation, memory B cells are susceptible to apoptosis but can be rescued via an antiapoptotic effect mediated through the Ras cascade...
- The in vivo pattern of binding of RAG1 and RAG2 to antigen receptor lociYanhong Ji
Department of Immunobiology, Yale University School of Medicine, 300 Cedar Street, Box 208011, New Haven, CT 06520 8011, USA
Cell 141:419-31. 2010The critical initial step in V(D)J recombination, binding of RAG1 and RAG2 to recombination signal sequences flanking antigen receptor V, D, and J gene segments, has not previously been characterized in vivo...
- Arthritogenic self-reactive CD4+ T cells acquire an FR4hiCD73hi anergic state in the presence of Foxp3+ regulatory T cellsRyan J Martinez
Department of Medicine, University of Minnesota Medical School, Minneapolis, MN 55455, USA
J Immunol 188:170-81. 2012..This suggests that autoimmune arthritis develops in the setting of lymphopenia when Foxp3(+)CD4(+) regulatory T cells are insufficient to functionally inactivate all autoreactive CD4(+) T cells that encounter self-Ag...
- A zinc site in the C-terminal domain of RAG1 is essential for DNA cleavage activityLORI M GWYN
Department of Biochemistry and Molecular Biology, The University of Oklahoma Health Sciences Center, Oklahoma City, 73190, USA
J Mol Biol 390:863-78. 2009The recombination-activating protein, RAG1, a key component of the V(D)J recombinase, binds multiple Zn(2+) ions in its catalytically required core region...
- Functional immunoglobulin transgenes guide ordered B-cell differentiation in Rag-1-deficient miceE Spanopoulou
Rockefeller University, New York, New York
Genes Dev 8:1030-42. 1994..These data also support the hypothesis that Rag-1 directly participates in the V(D)J recombination process...
- RAG mutations in human B cell-negative SCIDK Schwarz
Section of Molecular Biology, University of Ulm, D 89070 Ulm, Germany
Science 274:97-9. 1996..Six of 14 B- SCID patients tested were found to carry a mutation of the recombinase activating gene 1 (RAG-1), RAG-2, or both...
- Suppression of IL7Ralpha transcription by IL-7 and other prosurvival cytokines: a novel mechanism for maximizing IL-7-dependent T cell survivalJung Hyun Park
Experimental Immunology Branch, National Cancer Institute, Building 10 Room 4B36, Bethesda, Maryland 20892, USA
Immunity 21:289-302. 2004..We suggest that this homeostatic regulatory mechanism promotes survival of the maximum possible number of T cells for the amount of IL-7 available...
- TRAF6 is a T cell-intrinsic negative regulator required for the maintenance of immune homeostasisCarolyn G King
Department of Pathology and Laboratory Medicine, Abramson Family Cancer Research Institute, Philadelphia, Pennsylvania 19104, USA
Nat Med 12:1088-92. 2006..These data identify a previously unrecognized role for TRAF6 in the maintenance of peripheral tolerance, and suggest the presence of a T cell-intrinsic control mechanism to render responder T cells susceptible to tolerizing signals...
- Constitutive crosspresentation of tissue antigens by dendritic cells controls CD8+ T cell tolerance in vivoNancy Luckashenak
Institute for Immunology, Ludwig Maximilian University, 80336 Munich, Germany
Immunity 28:521-32. 2008..Thus, our data demonstrate the importance of crosstolerance induction by DCs as a vital instrument for controlling self-reactive T cells from the peripheral repertoire and preventing autoimmune disease...
- RAG-1 and ATM coordinate monoallelic recombination and nuclear positioning of immunoglobulin lociSusannah L Hewitt
Department of Pathology, New York University School of Medicine, New York, New York, USA
Nat Immunol 10:655-64. 2009..homologous immunoglobulin pairing was much lower in the absence of the RAG-1-RAG-2 recombinase and was restored in Rag1-/- developing B cells with a transgene expressing a RAG-1 active-site mutant that supported DNA binding but not ..
- Impaired V(D)J recombination and lymphocyte development in core RAG1-expressing miceDarryll D Dudley
Howard Hughes Medical Institute, The Children s Hospital, The Center for Blood Research, Harvard Medical School, Boston, MA 02115, USA
J Exp Med 198:1439-50. 2003b>RAG1 and RAG2 are the lymphocyte-specific components of the V(D)J recombinase. In vitro analyses of RAG function have relied on soluble, highly truncated "core" RAG proteins...
- An activated lck transgene promotes thymocyte development in RAG-1 mutant miceP Mombaerts
Howard Hughes Medical Institute, Department of Biology, Massachusetts Institute of Technology, Cambridge 02139
Immunity 1:261-7. 1994..In addition, p56lck may be involved in the down-regulation of the putative pre-TCR on CD4+CD8+ thymocytes...
- Overexpression of Bcl-2 in transgenic mice decreases apoptosis and improves survival in sepsisR S Hotchkiss
Department of Anesthesiology, Howard Hughes Medical Institute, Washington University School of Medicine, St Louis, MO 63110, USA
J Immunol 162:4148-56. 1999..We conclude that overexpression of Bcl-2 provides protection against cell death in sepsis. Lymphocyte death may be detrimental in sepsis by compromising host defense...
- The RAG1 N-terminal domain is an E3 ubiquitin ligaseVyacheslav Yurchenko
Department of Pathology, Albert Einstein College of Medicine, Bronx, New York 10461, USA
Genes Dev 17:581-5. 2003b>RAG1 and RAG2 initiate V(D)J recombination, which is the assembly of immunoglobulin and T cell receptor genes. The N-terminal region of RAG1 can be deleted, leaving an enzymatic "core" able to catalyze the complete reaction...
- IL-21 induces the functional maturation of murine NK cellsJason Brady
The Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria, Australia
J Immunol 172:2048-58. 2004..These developmental changes suggested that IL-21 functions to induce the terminal differentiation of mouse NK cells, resulting in heightened NK cell-mediated cytotoxicity and immune surveillance...
- Adaptive immune cells temper initial innate responsesKwang Dong Kim
Center for Infection and Immunity and National Laboratory of Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, 15 Da Tun Road, Chaoyang District, Beijing 100101, China
Nat Med 13:1248-52. 2007..Therefore, adaptive immune cells have an unexpected role in tempering initial innate responses...
- A WW-like module in the RAG1 N-terminal domain contributes to previously unidentified protein-protein interactionsRadhashree Maitra
Department of Pathology, Albert Einstein College of Medicine, Bronx, New York, 10461, USA
Nucleic Acids Res 37:3301-9. 2009More than one-third of the RAG1 protein can be truncated from the N-terminus with only subtle effects on the products of V(D)J recombination in vitro or in a mouse...
- The RING domain of RAG1 ubiquitylates histone H3: a novel activity in chromatin-mediated regulation of V(D)J joiningUrsula Grazini
Department of Experimental Oncology, European Institute of Oncology, Milan 20141, Italy
Mol Cell 37:282-93. 2010The RAG1 and RAG2 proteins are the only lymphoid-specific factors required to perform the first step of V(D)J recombination, DNA cleavage...
- Expansion of immunoglobulin-secreting cells and defects in B cell tolerance in Rag-dependent immunodeficiencyJolan E Walter
Division of Immunology and The Manton Center for Orphan Disease Research, Children s Hospital, Harvard Medical School, Boston, MA 02115, USA
J Exp Med 207:1541-54. 2010..We have studied a mut/mut mouse model of leaky SCID with a homozygous Rag1 S723C mutation that impairs, but does not abrogate, V(D)J recombination activity...
- Long-term T cell memory requires the surface expression of self-peptide/major histocompatibility complex moleculesM A Markiewicz
Gwen Knapp Center for Lupus and Immunology Research, The University of Chicago, Chicago, IL 60637, USA
Proc Natl Acad Sci U S A 95:3065-70. 1998..These data suggest that positive selection plays a role not only in T cell development but also in the maintenance of T cell memory...
- Rejection of H-Y disparate skin grafts by monospecific CD4+ Th1 and Th2 cells: no requirement for CD8+ T cells or B cellsD Zelenika
Therapeutic Immunology Group, Sir William Dunn School of Pathology, Oxford, United Kingdom
J Immunol 161:1868-74. 1998..Surprisingly, the transfer of either Th1 or Th2 CD4+ T cell lines from these mice into T cell-depleted recipients was sufficient to cause a specific rejection of male skin...
- Lymphotoxin alpha/beta and tumor necrosis factor are required for stromal cell expression of homing chemokines in B and T cell areas of the spleenV N Ngo
Department of Microbiology and Immunology, University of California San Francisco, San Francisco, California 94143, USA
J Exp Med 189:403-12. 1999..Together these findings indicate that LTalpha1beta2 and TNF are required for the development and function of B and T zone stromal cells that make chemokines necessary for lymphocyte compartmentalization in the spleen...
- Coordinate regulation of RAG1 and RAG2 by cell type-specific DNA elements 5' of RAG2W Yu
Laboratory of Molecular Immunology, Rockefeller University, 1230 York Avenue, New York, NY 10021, USA
Science 285:1080-4. 1999b>RAG1 and RAG2 are essential for V(D)J recombination and lymphocyte development. These genes are thought to encode a transposase derived from a mobile genetic element that was inserted into the vertebrate genome 450 million years ago...
- Following the development of a CD4 T cell response in vivo: from activation to memory formationS Garcia
Division of Molecular Immunology, The National Institute for Medical Research, Mill Hill, London, United Kingdom
Immunity 11:163-71. 1999..They differ qualitatively from naive T cells, suggesting that accelerated CD4 memory responses can occur without the need for increased frequencies of specific T cells...
- Mutational analysis of RAG1 and RAG2 identifies three catalytic amino acids in RAG1 critical for both cleavage steps of V(D)J recombinationM A Landree
Program in Cell and Molecular Biology, Baylor College of Medicine, Houston, Texas 77030, USA
Genes Dev 13:3059-69. 1999b>RAG1 and RAG2 initiate V(D)J recombination, the process of rearranging the antigen-binding domain of immunoglobulins and T-cell receptors, by introducing site-specific double-strand breaks (DSB) in chromosomal DNA during lymphocyte ..
- Mutations of acidic residues in RAG1 define the active site of the V(D)J recombinaseD R Kim
Molecular Biology Department, Massachusetts General Hospital, Boston, Massachusetts 02114, USA
Genes Dev 13:3070-80. 1999The RAG1 and RAG2 proteins collaborate to initiate V(D)J recombination by binding recombination signal sequences (RSSs) and making a double-strand break between the RSS and adjacent coding DNA...
- Normal thymic architecture and negative selection are associated with Aire expression, the gene defective in the autoimmune-polyendocrinopathy-candidiasis-ectodermal dystrophy (APECED)S Zuklys
Pediatric Immunology, The Children s University Hospital, Basel University, Basel, Switzerland
J Immunol 165:1976-83. 2000..Aire may determine thymic stromal organization and with it the induction of self-tolerance...
- Differential survival of naive CD4 and CD8 T cellsC Ferreira
Division of Molecular Immunology, National Institute for Medical Research, London, United Kingdom
J Immunol 165:3689-94. 2000..However, expression levels of Bcl-2 in either transgenic or polyclonal naive CD4 and CD8 T cells are similar, excluding a role for this molecule as a key factor in differential survival of CD4 vs CD8 T cells...
- The RAG proteins in V(D)J recombination: more than just a nucleaseM J Sadofsky
Medical College of Georgia, Institute of Molecular Medicine and Genetics, CB 2803, Augusta, GA 30912, USA
Nucleic Acids Res 29:1399-409. 2001..Two proteins, RAG1 and RAG2, together form the nuclease that cleaves the DNA at the border of the signal sequences...
- Increased accumulation of hybrid V(D)J joins in cells expressing truncated versus full-length RAGsJ A Sekiguchi
Howard Hughes Medical Institute, Harvard University Medical School, Boston, MA 02115, USA
Mol Cell 8:1383-90. 2001b>RAG1 and RAG2 (RAGs) initiate V(D)J recombination by introducing breaks between two coding segments and flanking recombination signals (RSs). Nonhomologous end-joining (NHEJ) proteins then join the coding segments and join the RSs...
- Impairment of immunological memory in the absence of MHC despite survival of memory T cellsGeorge Kassiotis
Division of Molecular Immunology, The National Institute for Medical Research, Mill Hill, London NW7 1AA, UK
Nat Immunol 3:244-50. 2002..Thus, in contrast to their survival, maintenance of the typical quality of memory T cells crucially depends on MHC-derived signals...
- Mutational analysis of all conserved basic amino acids in RAG-1 reveals catalytic, step arrest, and joining-deficient mutants in the V(D)J recombinaseLeslie E Huye
Department of Immunolog, Baylor College of Medicine, Houston, Texas 77030, USA
Mol Cell Biol 22:3460-73. 2002..Our analysis of these mutants provides insights into the molecular mechanisms underlying these disorders...
- Evidence of a critical architectural function for the RAG proteins in end processing, protection, and joining in V(D)J recombinationChia Lun Tsai
Department of Molecular Biophysics and Biochemistry, Section of Immunobiology, Yale University School of Medicine, New Haven, Connecticut 06510, USA
Genes Dev 16:1934-49. 2002..We have identified RAG1 mutants that are proficient in DNA cleavage but defective in their ability to interact with coding ends after ..
- During the early prediabetic period in NOD mice, the pathogenic CD8(+) T-cell population comprises multiple antigenic specificitiesTeresa P DiLorenzo
Department of Microbiology and Infectious Diseases, Faculty of Medicine, University of Calgary, Calgary, Alberta, T2N 4N1, Canada
Clin Immunol 105:332-41. 2002..NIT-1 cells represent an unlimited peptide source that will allow for the future isolation and sequencing of the novel multiple epitopes targeted early in the autoimmune response by pathogenic CD8(+) T cells...
- The resolution of relapsing fever borreliosis requires IgM and is concurrent with expansion of B1b lymphocytesKishore R Alugupalli
Department of Molecular Genetics and Microbiology, University of Massachusetts Medical School, Worcester, MA 01655, USA
J Immunol 170:3819-27. 2003..hermsii. Together these results support the model that B1b cells generate the T-independent IgM required for the control and resolution of relapsing fever borreliosis...
- Immune complex-dependent remodeling of the airway vasculature in response to a chronic bacterial infectionArin B Aurora
Department of Microbiology and Immunology, University of California, San Francisco, CA 94143, USA
J Immunol 175:6319-26. 2005..The results reveal a novel pathway whereby T cell-dependent humoral immunity to a persistent airway infection can induce inflammation-dependent angiogenesis, lymphangiogenesis, and chronic airway pathology...
- An intersection between the self-reactive regulatory and nonregulatory T cell receptor repertoiresChyi Song Hsieh
Department of Medicine and Division of Rheumatology, University of Washington, Seattle, Washington 98195, USA
Nat Immunol 7:401-10. 2006..Our analyses suggest that T(reg) cells and potentially pathogenic autoimmune T cells use overlapping pools of self-reactive TCRs...
- Interleukin 25 regulates type 2 cytokine-dependent immunity and limits chronic inflammation in the gastrointestinal tractAlexander M Owyang
Department of Pathobiology, University of Pennsylvania, Philadelphia, PA 19104, USA
J Exp Med 203:843-9. 2006..Therefore, IL-25 is not only a critical mediator of type 2 immunity, but is also required for the regulation of inflammation in the gastrointestinal tract...
- Antigen-induced IL-10+ regulatory T cells are independent of CD25+ regulatory cells for their growth, differentiation, and functionKirsty S Nicolson
Department of Cellular and Molecular Medicine, University of Bristol Medical School, University Walk, Bristol, United Kingdom
J Immunol 176:5329-37. 2006..These results demonstrate that these natural and induced regulatory cells fall into distinct subsets...
- Lymphocyte recruitment into the aortic wall before and during development of atherosclerosis is partially L-selectin dependentElena Galkina
Department of Biomedical Engineering, University of Virginia, Health Sciences Center, Charlottesville, VA 22908, USA
J Exp Med 203:1273-82. 2006..Atherosclerosis induces the recruitment of macrophages and dendritic cells that support antigen presentation...
- RANK signals from CD4(+)3(-) inducer cells regulate development of Aire-expressing epithelial cells in the thymic medullaSimona W Rossi
Medical Research Council Centre for Immune Regulation, Institute for Biomedical Research, University of Birmingham, B15 2TT Birmingham, UK
J Exp Med 204:1267-72. 2007..Collectively, our data reveal cellular and molecular mechanisms leading to the generation of Aire(+) mTECs and highlight a previously unrecognized role for CD4(+)3(-)RANKL(+) inducer cells in intrathymic self-tolerance...
- Survival of lethal poxvirus infection in mice depends on TLR9, and therapeutic vaccination provides protectionChristofer Samuelsson
Department of Research, Bavarian Nordic, Martinsried, Germany
J Clin Invest 118:1776-84. 2008..Therefore, these data suggest an essential role for TLR9 in the defense against poxviruses. In addition, postexposure application of MVA may protect against lethal poxvirus infection...
- High incidence of spontaneous autoimmune encephalomyelitis in immunodeficient anti-myelin basic protein T cell receptor transgenic miceJ J Lafaille
Howard Hughes Medical Institute, Department of Biology, Massachusetts Institute of Technology, Cambridge 02139
Cell 78:399-408. 1994..The data also suggest that spontaneous EAE may be triggered by an in situ activation of CD4+ anti-MBP cells in the nervous system...
- A regulatory role for recombinase activating genes, RAG-1 and RAG-2, in T cell developmentJ Wayne
Howard Hughes Medical Institute, Rockefeller University, New York, New York 10021
Immunity 1:95-107. 1994..We propose that in addition to a previously documented role in V(D)J recombination, RAG-1 and RAG-2 expression must be properly regulated for completion of normal T cell development..
- Fyn can partially substitute for Lck in T lymphocyte developmentT Groves
Division of Immunology and Cancer, Hospital for Sick Children Research Institute, Toronto, Ontario, Canada
Immunity 5:417-28. 1996..These observations reveal that Fyn can subserve some Lck-like functions in T cell development...
- Definition of a large region of RAG1 that is important for coimmunoprecipitation of RAG2C J McMahan
Section of Immunobiology, Yale University School of Medicine, New Haven, CT 06520, USA
J Immunol 158:2202-10. 1997Interaction between the RAG1 and RAG2 proteins is probably critical for V(D)J recombination. Using a coimmunoprecipitation assay, we define a large region of RAG1 (amino acids 504-1008) that is sufficient for interaction with RAG2...
- Bcl-2 can rescue T lymphocyte development in interleukin-7 receptor-deficient mice but not in mutant rag-1-/- miceE Maraskovsky
Department of Cellular Immunology, Immunex Research and Development Corporation, Seattle, Washington 98101, USA
Cell 89:1011-9. 1997..These results provide evidence that blocking apoptosis is the essential function of IL-7R during differentiation and activation of T lymphocytes and that pre-TCR signaling blocks a pathway to apoptosis that is insensitive to Bcl-2...
- Pre-TCR signaling and inactivation of p53 induces crucial cell survival pathways in pre-T cellsM C Haks
Division of Immunology, The Netherlands Cancer Institute, Amsterdam
Immunity 11:91-101. 1999..In addition, the CD4+ CD8+ (DP) compartment is expanded to its normal size. These findings suggest that the pre-TCR regulates progression through the DNA-damage checkpoint of the DN to DP transition by inactivating p53...
- Continued RAG expression in late stages of B cell development and no apparent re-induction after immunizationW Yu
Laboratory of Molecular Immunology, The Rockefeller University, New York, New York 10021, USA
Nature 400:682-7. 1999..Our findings may help to reconcile a series of apparently contradictory observations, and suggest a new model for the mechanisms that regulate allelic exclusion, receptor editing and tolerance...
- The requirement of membrane lymphotoxin for the presence of dendritic cells in lymphoid tissuesQ Wu
Department of Pathology, The University of Chicago, Chicago, Illinois 60637, USA
J Exp Med 190:629-38. 1999..Taken together, these results support the notion that the signaling via LTbetaR by membrane LTalpha/beta is required for the presence of DCs in lymphoid tissues...
- Homeostasis and anergy of CD4(+)CD25(+) suppressor T cells in vivoMarc A Gavin
Howard Hughes Medical Institute, University of Washington, Box 357370, Seattle, WA 98195, USA
Nat Immunol 3:33-41. 2002..DNA array analyses identified genes that may inhibit responsiveness at a number of levels in multiple signaling cascades in T(S) cells, as well as several anti-apoptotic genes that may mediate their survival...
- Transcription from the RAG1 locus marks the earliest lymphocyte progenitors in bone marrowHideya Igarashi
Immunobiology and Cancer Program, Oklahoma Medical Research Foundation, 825 Northeast 13th Street, Oklahoma City 73104, USA
Immunity 17:117-30. 2002Viable Lin(-) CD27(+) c-kit(Hi) Sca-1(Hi) GFP(+) cells recovered from heterozygous RAG1/GFP knockin mice progressed through previously defined stages of B, T, and NK cell lineage differentiation...
- Spontaneous proliferation, a response of naive CD4 T cells determined by the diversity of the memory cell repertoireBooki Min
Laboratory of Immunology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892 1892, USA
Proc Natl Acad Sci U S A 101:3874-9. 2004..This finding suggests that the immune system has evolved mechanisms to attain a memory cell repertoire of great diversity independently of foreign antigens...
- IFN-gamma determines distinct clinical outcomes in autoimmune encephalomyelitisAllen K Wensky
Molecular Pathogenesis Program, Skirball Institute of Biomolecular Medicine, New York University Medical Center, New York, NY 10016, USA
J Immunol 174:1416-23. 2005....
- CD8+ T cell immunity against a tumor/self-antigen is augmented by CD4+ T helper cells and hindered by naturally occurring T regulatory cellsPaul A Antony
Division of Surgery, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA
J Immunol 174:2591-601. 2005..These findings reveal that Th cells can help break tolerance to a persisting self-Ag and treat established tumors through an IL-2-dependent mechanism, but requires simultaneous absence of naturally occurring T(reg) cells to be effective...
- Lineage-specific requirement for the PH domain of Vav1 in the activation of CD4+ but not CD8+ T cellsAntonella Prisco
Division of Immune Cell Biology, National Institute for Medical Research, The Ridgeway, Mill Hill, London NW7 1AA, UK
Immunity 23:263-74. 2005..Unexpectedly, the mutation selectively affects TCR-induced proliferation of CD4(+) but not CD8(+) T cells, demonstrating differences in the wiring of TCR signaling pathways between the two lineages...
- Transgenic insulin (B:9-23) T-cell receptor mice develop autoimmune diabetes dependent upon RAG genotype, H-2g7 homozygosity, and insulin 2 gene knockoutJean M Jasinski
Barbara Davis Center for Childhood Diabetes, University of Colorado Health Sciences Center, P O Box 6511, MS B140, Aurora, CO 80045 6511, USA
Diabetes 55:1978-84. 2006..scid mouse. The current study demonstrates that the BDC12-4.1 TCR is sufficient to cause diabetes at NOD backcross 1, bypassing polygenic inhibition of insulitis and diabetogenesis...
- Unique maturation program of the IgE response in vivoAgustin Erazo
Program of Molecular Pathogenesis, Skirball Institute of Biomolecular Medicine, New York University School of Medicine, New York, NY 10016, USA
Immunity 26:191-203. 2007..Our results have implications for the understanding of IgE memory responses in allergy...
- Mice lacking components of adaptive immunity show increased Brucella abortus virB mutant colonizationHortensia García Rolán
Department of Medical Microbiology and Immunology, University of California, One Shields Avenue, Davis, CA 95616, USA
Infect Immun 75:2965-73. 2007..However, spleens of Rag1(-/-) mice and Igh6(-/-) mice were more highly colonized by the virB mutant than control mice after 14 to 21 days, ..
- Rag mutations reveal robust alternative end joiningBarbara Corneo
The Kimmel Center for Biology and Medicine of the Skirball Institute and Department of Pathology, New York University School of Medicine, New York, New York 10016, USA
Nature 449:483-6. 2007..mechanism for generating diversity in antigen receptors, relies on NHEJ for repairing DSBs introduced by the Rag1-Rag2 protein complex. Animals lacking any of the seven known NHEJ factors are therefore immunodeficient...
- Tumor-specific Th17-polarized cells eradicate large established melanomaPawel Muranski
Center for Cancer Research, National Cancer Institute, National Institutes of Health, Mark O Hatfield Clinical Research Center, Bethesda, MD 20892, USA
Blood 112:362-73. 2008..This principle should be considered in designing clinical trials involving adoptive transfer-based immunotherapy of human malignancies...
- Foxo1 directly regulates the transcription of recombination-activating genes during B cell developmentRupesh H Amin
Department of Molecular and Cell Biology, University of California at Berkeley, Berkeley, California 94720, USA
Nat Immunol 9:613-22. 2008..Foxo1 directly activated transcription of the Rag1-Rag2 locus throughout early B cell development, and a decrease in Foxo1 protein diminished the induction of Rag1 ..
- TGF-beta signaling in dendritic cells is a prerequisite for the control of autoimmune encephalomyelitisYasmina Laouar
Department of Immunobiology, Yale University School of Medicine, New Haven, CT 06520, USA
Proc Natl Acad Sci U S A 105:10865-70. 2008..Our data provide direct evidence that TGF-beta can control autoimmunity via actions on DCs...
- B lymphocyte activation by coinfection prevents immune control of friend virus infectionRute Marques
Division of Immunoregulation, Medical Research Council National Institute for Medical Research, London, United Kingdom
J Immunol 181:3432-40. 2008..Thus, immune activation by coinfecting pathogens or their products can contribute to the pathogenicity of retroviral infection...
- Plasminogen activator inhibitor-1 protects endothelial cells from FasL-mediated apoptosisKhalid Bajou
Division of Hematology Oncology, Department of Pediatrics, University of Southern California and The Saban Research Institute of Childrens Hospital Los Angeles, Los Angeles, CA 90027, USA
Cancer Cell 14:324-34. 2008..We further demonstrate that plasmin cleaves FasL at Arg144-Lys145, releasing a soluble proapoptotic FasL fragment from the surface of ECs. The data provide a mechanism explaining the proangiogenic activity of PAI-1...
- Soluble frizzled-related protein 1 is estrogen inducible in bone marrow stromal cells and suppresses the earliest events in lymphopoiesisTakafumi Yokota
Department of Hematology and Oncology, Osaka University Graduate School of Medicine, Suita, Osaka, Japan
J Immunol 181:6061-72. 2008..We now confirm with Rag1/GFP reporter mice that early lymphoid progenitors in the lineage marker(-) c-kit(high) ScaI(+), hematopoietic stem ..
- West Nile virus-specific CD4 T cells exhibit direct antiviral cytokine secretion and cytotoxicity and are sufficient for antiviral protectionJames D Brien
Department of Molecular Microbiology and Immunology, Oregon National Primate Research Center, Vaccine and Gene Therapy Institute, Oregon Health and Science University, Beaverton, OR 97006, USA
J Immunol 181:8568-75. 2008..These results demonstrate the role of direct effector function of Ag-specific CD4 T cells in preventing severe WNV disease...
- Leaky severe combined immunodeficiency and aberrant DNA rearrangements due to a hypomorphic RAG1 mutationWilliam Giblin
Department of Internal Medicine, University of Michigan, Ann Arbor, MI 48109, USA
Blood 113:2965-75. 2009The RAG1/2 endonuclease initiates programmed DNA rearrangements in progenitor lymphocytes by generating double-strand breaks at specific recombination signal sequences...
- Structure of the RAG1 nonamer binding domain with DNA reveals a dimer that mediates DNA synapsisFang Fang Yin
Department of Molecular Biophysics and Biochemistry, Yale University, New Haven, Connecticut, USA
Nat Struct Mol Biol 16:499-508. 2009The products of recombination-activating genes RAG1 and RAG2 mediate the assembly of antigen receptor genes during lymphocyte development in a process known as V(D)J recombination...
- Impaired lymphocyte development and antibody class switching and increased malignancy in a murine model of DNA ligase IV syndromeAnastasia Nijnik
Henry Wellcome Building of Molecular Physiology, Oxford University, Oxford, United Kingdom
J Clin Invest 119:1696-705. 2009..These findings provide explanations for the complex lymphoid phenotype of human LigIV syndrome...
- The receptor S1P1 overrides regulatory T cell-mediated immune suppression through Akt-mTORGuangwei Liu
Department of Immunology, St Jude Children s Research Hospital, Memphis, Tennessee, USA
Nat Immunol 10:769-77. 2009..Dynamic regulation of S1P1 contributed to lymphocyte priming and immune homeostasis. Thus, by antagonizing T(reg) cell-mediated immune suppression, the lipid-activated S1P1-Akt-mTOR pathway orchestrates adaptive immune responses...
- Transcriptional repressor Blimp-1 promotes CD8(+) T cell terminal differentiation and represses the acquisition of central memory T cell propertiesRachel L Rutishauser
Department of Immunobiology, Yale University School of Medicine, New Haven, CT 06520, USA
Immunity 31:296-308. 2009..These results reveal a critical role for Blimp-1 in controlling terminal differentiation and suppressing memory cell developmental potential in effector CD8(+) T cells during viral infection...
- Naive tumor-specific CD4(+) T cells differentiated in vivo eradicate established melanomaYing Xie
Program in Molecular Microbiology and Immunology, University of Maryland School of Medicine, Baltimore, MD 21201, USA
J Exp Med 207:651-67. 2010..Thus, these data provide a platform for designing immunotherapies that incorporate tumor/self-reactive CD4(+) T cells...
- The RAG2 C terminus suppresses genomic instability and lymphomagenesisLudovic Deriano
Department of Pathology, New York University School of Medicine, New York, NY 10016, USA
Nature 471:119-23. 2011Misrepair of DNA double-strand breaks produced by the V(D)J recombinase (the RAG1/RAG2 proteins) at immunoglobulin (Ig) and T cell receptor (Tcr) loci has been implicated in pathogenesis of lymphoid malignancies in humans and in mice...
- The P4-type ATPase ATP11C is essential for B lymphopoiesis in adult bone marrowOwen M Siggs
Department of Genetics, The Scripps Research Institute, La Jolla, California, USA
Nat Immunol 12:434-40. 2011..Our data establish an essential, cell-autonomous and context-sensitive function for ATP11C, a putative aminophospholipid flippase, in B cell development...
- Silencing suppressor of cytokine signaling-1 (SOCS1) in macrophages improves Mycobacterium tuberculosis control in an interferon-gamma (IFN-gamma)-dependent mannerBerit Carow
Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, Stockholm 17177, Sweden
J Biol Chem 286:26873-87. 2011..tuberculosis clearance early after infection in vivo in an IFN-γ-dependent manner. On the other hand, at later time points, SOCS1 expression by non-macrophage cells protected the host from infection-induced detrimental inflammation...
- NEW MOUSE MODELS OF DIABESITYEdward Leiter; Fiscal Year: 2002..Collectively, these studies will permit genetic and metabolic characterization of key events in the transition from simple obesity to diabesity in thee novel mouse models. ..
- New Insights into Animals Models of DiabetesEdward Leiter; Fiscal Year: 2003..The meeting is planned for 200 participants. Because of limited seating capacity in The Jackson Laboratory's auditorium, the meeting venue will be the Bar Harbor Regency Hotel, where participants will be housed and fed. ..
- PATHOGENESIS OF AUTOIMMUNE DIABETES IN MICEEdward Leiter; Fiscal Year: 2004..Understanding the contributions of diabetes modifying genes in the extended mouse MIHC may identify human HLA orthologs whose presence has recently been established. ..
- GENETICS AND PATHOLOGY OF NON-OBESE DIABETIC (NOD) MICEEdward Leiter; Fiscal Year: 2005..These latter investigations are of particular importance in view of an ongoing NIDDK trial to prevent T1D in humans deemed at high risk by oral insulin treatment. ..
- Natural Killer Cell Mediated Control of Vaccinia VirusAnthony French; Fiscal Year: 2007..The proposed work will occur under the mentorship of Dr. Wayne Yokoyama a recognized pioneer in the NK cell field who has successfully trained numerous graduate students and postdoctoral fellows. [unreadable] [unreadable]..
- Early T cell checkpoint violation in NOD miceMary A Yui; Fiscal Year: 2010..Identifying genes and pathways affectingT cells, which predispose NOD mice to T1D will help in the understanding of immune deviations that can lead to disease in humans. ..
- TNF Receptors of Colonic Epithelial Cells in IBDEmiko Mizoguchi; Fiscal Year: 2007..Daniel K. Podolsky from the Division of Gastroenterology and by Dr. Atul K. Bhan from the Immunopathology Unit, both at Massachusetts General Hospital and Harvard Medical School. ..
- Regulatory Role of TNFR1 in Inflammatory Bowel DiseaseEmiko Mizoguchi; Fiscal Year: 2007..We believe the data obtained from this study would provide an important rationale to develop new TNF related therapeutic approaches for human IBD. [unreadable] [unreadable] [unreadable]..
- Regulation of Osteoclast Differentiation by Pax5Mark Horowitz; Fiscal Year: 2007..Such information would be applicable to a wide variety of skeletal defects including, post-menopausal osteoporosis, age-related osteopenia, fracture repair, and extended survival of prosthetic implants. ..
- CD8 T Cell Reactivity to IGRP as an Autoimmunity Marker in Type 1 DiabetesTeresa Dilorenzo; Fiscal Year: 2007..Tests may also be developed to monitor destructive T cell activity in patients undergoing treatment, so that doctors will be able to know if the treatments are working. [unreadable] [unreadable] [unreadable]..
- SiRNA Gene Therapy for HIV/AIDSRamesh Akkina; Fiscal Year: 2008..4. Transduce siRNA constructs into the newly described CD34+/KDR+ primitive hematopoietic progenitor cells and derive macrophages in vitro and thymocytes in vivo, and evaluate their HIV-1 resistance. [unreadable] [unreadable]..
- REGULATION OF BONE REMODELING BY MEGAKARYOCYTESMark Horowitz; Fiscal Year: 2009..Such information would be applicable to a wide variety of skeletal defects including, post-menopausal osteoporosis, age-related osteopenia, fracture repair, and extended survival of prosthetic implants. ..
- Genomic dissection of platelet productionWarren Alexander; Fiscal Year: 2009....
- Immunological control of a persistent viral infectionSally R Sarawar; Fiscal Year: 2010..The results obtained may have broader significance in understanding the mechanisms controlling T cell activation or tolerance, in general. ..
- ANALYSIS OF THE MURINE ANTIBODY REPERTOIREGARNETT H KELSOE; Fiscal Year: 2010..of B cells that initiatelsupport receptor editing;2) the role of self-antigens in the induction of regulated RAG 1/2 expression and rearrangement, and;3) the selection criteria that might determine clonal tolerance/selection ..
- CONTROL OF OSTEOGENESIS AND ADIPOGENESIS BY EBFMark C Horowitz; Fiscal Year: 2010..Such information would be applicable to a wide variety of skeletal defects including age-related osteopenia, post-menopausal osteoporosis, fracture repair, and extended survival of prosthetic implants. ..
- REGULATION OF HEMATOPOIESIS BY THROMBOPOIETINWarren Alexander; Fiscal Year: 2001..abstract_text> ..
- Mouse Models of Tumor Progression and Therapy ResponseCHRISTOPHER KEMP; Fiscal Year: 2007..These experiments will reveal the molecular and cellular basis for the poor clinical outcome associated with p27 deficient tumors. This knowledge can then be applied to improve treatment design and regimen in the clinical setting. ..
- The antigen specificity of CD25+ CD4+ T regulatory cellsCHYI HSIEH; Fiscal Year: 2005..Understanding the antigen specificity of this important endogenous T cell suppressor may facilitate the development of disease specific treatments without broad immuno-suppressive side effects. ..
- Akt activation sustains silica induced inflammationCELINE BEAMER; Fiscal Year: 2006..abstract_text> ..
- The Role of Double Strand Breaks in CarcinogenesisCHRISTOPHER KEMP; Fiscal Year: 2006..Understanding the functional interaction of the P13 Ks, in regulating p53, apoptosis, development and carcinogenesis at the level of the whole animal is a necessary link to apply knowledge gained from cell culture models to the clinic. ..
- Modeling RNA-based HIV gene therapeutics in SCID-hu miceRamesh Akkina; Fiscal Year: 2006..4) Determine the engraftment and thymopoietic potential of lentivirally transduced primitive hematopoietic precursor cells i.e., a) CD34+ and KDR+ cells, b) SP cells in the SCID-hu mouse thymic microenvironment. ..
- B Cell Expansion After Dendritic Cell ImmunizationMichael Jordan; Fiscal Year: 2004..My near term career path will involve ongoing basic research and study in order to improve my ultimate scientific productivity. ..
- Prevention of Diabetes with Lipid ImmunomodulatorsTeresa Dilorenzo; Fiscal Year: 2005....
- Role of BCL-6 in Allergic Immune ResponsesAlexander Dent; Fiscal Year: 2005..These studies will also provide insight into the function of BCL6, which may help the treatment of B cell lymphoma. ..
- THE ROLE OF COMPLEMENT IN AUTOIMMUNITYGarnett Kelsoe; Fiscal Year: 2005..Thus, we propose that the innate immune system controls both the frequency of peripheral, self-reactive B cells and their exposure to antigen. ..
- CHEMOKINES IN THE IMMUNE RESPONSE TO A VIRAL INFECTIONSally Sarawar; Fiscal Year: 2002..3) The role of the CXCR2 chemokine receptor homologue in viral pathogenesis will be determined using a mutant virus in which the gene encoding the CXCR2 homologue has been inactivated. ..
- COMPLEMENT AND B CELL TOLERANCE IN A MURINE MODEL OF SLEElahna Paul; Fiscal Year: 2002..By combining immunologic, nephrologic and molecular analyses I propose to elucidate how classical complement deficiency predisposes to SLE. ..
- The stress of dry eye on corneal barrier functionCINTIA DE PAIVA; Fiscal Year: 2006..TJ and LEP expression will be evaluated by laser scanning confocal microscopy and immunostaining. Pro inflammatory mediator expression will be evaluated by Western Blot, ELISA and the Luminex Multiplex Assay. [unreadable] [unreadable]..
- Interaction between influenza virus and H. influenzaeSally Sarawar; Fiscal Year: 2007..This could be particularly important during an influenza pandemic and may be more broadly applicable to other respiratory viruses. [unreadable] [unreadable] [unreadable]..
- Anti-Tumor Autoimmunity by lymphopenia T cell ExpansionRoberto Baccala; Fiscal Year: 2008..The results will define the role of homeostatic T cell proliferation in tumor autoimmunity, and provide new approaches to the treatment of cancer. [unreadable] [unreadable]..
- Gene expression in non-functional CD8 T cellsSally Sarawar; Fiscal Year: 2005..The data are likely to lead to a new understanding of how CD8 T cells function in the control of persistent viral infections and mechanisms of CD8 T cell activation. ..