J A Bluestone

Summary

Affiliation: University of California
Country: USA

Publications

  1. ncbi request reprint Cutting edge: CD28 controls peripheral homeostasis of CD4+CD25+ regulatory T cells
    Qizhi Tang
    University of California San Francisco Diabetes Center, University of California, San Francisco, CA 94143, USA
    J Immunol 171:3348-52. 2003
  2. ncbi request reprint How do CD4+CD25+ regulatory T cells control autoimmunity?
    Jeffrey A Bluestone
    University of California at San Francisco Diabetes Center, Department of Medicine, University of California, San Francisco, 513 Parnassus Avenue, San Francisco, California 94143 0540, USA
    Curr Opin Immunol 17:638-42. 2005
  3. pmc Development of spontaneous autoimmune peripheral polyneuropathy in B7-2-deficient NOD mice
    B Salomon
    The Committee on Immunology, University of Chicago, Chicago, IL 60637, USA
    J Exp Med 194:677-84. 2001
  4. doi request reprint T regulatory cells in autoimmune diabetes: past challenges, future prospects
    Jeffrey A Bluestone
    UCSF Diabetes Center, San Francisco, CA 94143, USA
    J Clin Immunol 28:677-84. 2008
  5. ncbi request reprint Natural versus adaptive regulatory T cells
    Jeffrey A Bluestone
    Diabetes Research Center, University of California, San Francisco, California 94118, USA
    Nat Rev Immunol 3:253-7. 2003
  6. pmc The effect of costimulatory and interleukin 2 receptor blockade on regulatory T cells in renal transplantation
    J A Bluestone
    Diabetes Center, Department of Medicine, University of California San Francisco, CA, USA
    Am J Transplant 8:2086-96. 2008
  7. pmc Therapeutic vaccination using CD4+CD25+ antigen-specific regulatory T cells
    Jeffrey A Bluestone
    Diabetes Center, Department of Medicine, University of California, San Francisco, CA 94143 0540, USA
    Proc Natl Acad Sci U S A 101:14622-6. 2004
  8. ncbi request reprint Genetics, pathogenesis and clinical interventions in type 1 diabetes
    Jeffrey A Bluestone
    Diabetes Center and the Department of Medicine, University of California, San Francisco, San Francisco, California 94143, USA
    Nature 464:1293-300. 2010
  9. pmc The functional plasticity of T cell subsets
    Jeffrey A Bluestone
    University of California, San Francisco Diabetes Center and Department of Medicine, University of California, San Francisco 513 Parnassus Avenue, Box 0540 HSW 1114, San Francisco, California 94143, USA
    Nat Rev Immunol 9:811-6. 2009
  10. ncbi request reprint CTLA4Ig inhibits airway eosinophilia and hyperresponsiveness by regulating the development of Th1/Th2 subsets in a murine model of asthma
    P A Padrid
    Department of Medicine, University of Chicago, Chicago, Illinois 60637, USA
    Am J Respir Cell Mol Biol 18:453-62. 1998

Research Grants

  1. Conf on Mechanism and Applications of Immune Tolerance
    Jeffrey Bluestone; Fiscal Year: 2002
  2. Role of Notch 1 in Immune Tolerance
    Jeffrey Bluestone; Fiscal Year: 2005
  3. IMMUNOMODULATION OF TRANSPLANT REJECTION BY ANTI-CD3 MAB
    Jeffrey Bluestone; Fiscal Year: 2007

Detail Information

Publications99

  1. ncbi request reprint Cutting edge: CD28 controls peripheral homeostasis of CD4+CD25+ regulatory T cells
    Qizhi Tang
    University of California San Francisco Diabetes Center, University of California, San Francisco, CA 94143, USA
    J Immunol 171:3348-52. 2003
    ..CD28 maintains a stable pool of peripheral Tregs by both supporting their survival and promoting their self-renewal. CD28 engagement promotes survival by regulating IL-2 production by conventional T cells and CD25 expression on Tregs...
  2. ncbi request reprint How do CD4+CD25+ regulatory T cells control autoimmunity?
    Jeffrey A Bluestone
    University of California at San Francisco Diabetes Center, Department of Medicine, University of California, San Francisco, 513 Parnassus Avenue, San Francisco, California 94143 0540, USA
    Curr Opin Immunol 17:638-42. 2005
    ..Recent in vivo analyses support a model in which Tregs directly or indirectly alter the activation and differentiation of pathogenic T cells through an effect on antigen presenting cells...
  3. pmc Development of spontaneous autoimmune peripheral polyneuropathy in B7-2-deficient NOD mice
    B Salomon
    The Committee on Immunology, University of Chicago, Chicago, IL 60637, USA
    J Exp Med 194:677-84. 2001
    ..This model demonstrates that NOD mice have "cryptic" autoimmune defects that can polarize toward the nervous tissue after the selective disruption of CD28/B7-2 costimulatory pathway...
  4. doi request reprint T regulatory cells in autoimmune diabetes: past challenges, future prospects
    Jeffrey A Bluestone
    UCSF Diabetes Center, San Francisco, CA 94143, USA
    J Clin Immunol 28:677-84. 2008
    ..The development of type 1 diabetes in the NOD mouse strain it is a complex process that depends on a fine balance between pathogenic and regulatory pathways...
  5. ncbi request reprint Natural versus adaptive regulatory T cells
    Jeffrey A Bluestone
    Diabetes Research Center, University of California, San Francisco, California 94118, USA
    Nat Rev Immunol 3:253-7. 2003
    ..Here, we propose the existence of two subsets of CD4+ T(Reg) cells--natural and adaptive--that differ in terms of their development, specificity, mechanism of action and dependence on T-cell receptor and co-stimulatory signalling...
  6. pmc The effect of costimulatory and interleukin 2 receptor blockade on regulatory T cells in renal transplantation
    J A Bluestone
    Diabetes Center, Department of Medicine, University of California San Francisco, CA, USA
    Am J Transplant 8:2086-96. 2008
    ....
  7. pmc Therapeutic vaccination using CD4+CD25+ antigen-specific regulatory T cells
    Jeffrey A Bluestone
    Diabetes Center, Department of Medicine, University of California, San Francisco, CA 94143 0540, USA
    Proc Natl Acad Sci U S A 101:14622-6. 2004
    ..Emphasis will be placed on approaches to exploit regulatory T cells either directly or through the use of anti-CD3 immunotherapy...
  8. ncbi request reprint Genetics, pathogenesis and clinical interventions in type 1 diabetes
    Jeffrey A Bluestone
    Diabetes Center and the Department of Medicine, University of California, San Francisco, San Francisco, California 94143, USA
    Nature 464:1293-300. 2010
    ..Here we describe current progress, the challenges ahead and the new interventions that are being tested to address the unmet need for preventative or curative therapies...
  9. pmc The functional plasticity of T cell subsets
    Jeffrey A Bluestone
    University of California, San Francisco Diabetes Center and Department of Medicine, University of California, San Francisco 513 Parnassus Avenue, Box 0540 HSW 1114, San Francisco, California 94143, USA
    Nat Rev Immunol 9:811-6. 2009
    ..Here, Nature Reviews Immunology asks four leaders in the field their thoughts on the functional plasticity of T cell subsets...
  10. ncbi request reprint CTLA4Ig inhibits airway eosinophilia and hyperresponsiveness by regulating the development of Th1/Th2 subsets in a murine model of asthma
    P A Padrid
    Department of Medicine, University of Chicago, Chicago, Illinois 60637, USA
    Am J Respir Cell Mol Biol 18:453-62. 1998
    ..mansoni-sensitized and airway-challenged mice, most likely due to attenuated secretion of Th2-type cytokines and increased secretion of Th1-type cytokines...
  11. ncbi request reprint Inducible costimulator regulates Th2-mediated inflammation, but not Th2 differentiation, in a model of allergic airway disease
    A G Tesciuba
    Committee on Immunology and Section of Pulmonary and Critical Care, Department of Medicine, and Ben May Institute for Cancer Research, University of Chicago, Chicago, IL, 60637, USA
    J Immunol 167:1996-2003. 2001
    ..Thus, blockade of ICOS signaling can significantly reduce airway inflammation without affecting Th2 differentiation in this model of allergic airway disease...
  12. pmc Signaling through CD28 and CTLA-4 controls two distinct forms of T cell anergy
    A D Wells
    Department of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania 19104 6144, USA
    J Clin Invest 108:895-903. 2001
    ..Anergy may be induced either through a combination of CTLA-4 signaling and the failure of cell cycle progression, or through a proliferation-independent mechanism in which TCR ligation occurs in the absence of CD28...
  13. ncbi request reprint Role of STAT4 and STAT6 signaling in allograft rejection and CTLA4-Ig-mediated tolerance
    P Zhou
    Section of Transplantation, Departments of Surgery, Section of Rheumatology, Department of Medicine, University of Chicago, Chicago, IL 60637, USA
    J Immunol 165:5580-7. 2000
    ..These data suggest that the balance of type 1 and type 2 T lymphocyte differentiation is not critical for acute rejection but influences the robust tolerance induced by CD28/B7 blockade in this model...
  14. ncbi request reprint ICOS costimulation: It's not just for TH2 cells anymore
    A I Sperling
    Section of Pulmonary and Critical Care Medicine, Department of Medicine, and the Committee on Immunology, University of Chicago, Chicago, IL 60637, USA
    Nat Immunol 2:573-4. 2001
    ..A current paradigm has ICOS participating in TH2 costimulation. New data indicates ICOS regulates not only TH2 cells, but also TH1s...
  15. ncbi request reprint In vitro expanded human CD4+CD25+ regulatory T cells suppress effector T cell proliferation
    K E Earle
    Department of Medicine, UCSF Diabetes Center, University of California, Box 0540, 513 Parnassus Avenue, San Francisco, CA 94143 0540, USA
    Clin Immunol 115:3-9. 2005
    ..Treg expansion is a critical first step before consideration of Tregs as a therapeutic intervention in patients with autoimmune or graft-versus-host disease...
  16. pmc Costimulation controls diabetes by altering the balance of pathogenic and regulatory T cells
    Helene Bour-Jordan
    UCSF Diabetes Center, University of California at San Francisco, San Francisco, California 94143, USA
    J Clin Invest 114:979-87. 2004
    ..Thus, elimination of Treg's results in diabetes even in the absence of costimulation, which suggests a need for alternative strategies for immunotherapeutic approaches...
  17. pmc Interactions between PD-1 and PD-L1 promote tolerance by blocking the TCR-induced stop signal
    Brian T Fife
    UCSF Diabetes Center, Department of Medicine, University of California, San Francisco, California, USA
    Nat Immunol 10:1185-92. 2009
    ..Blockade of the immunomodulatory receptor CTLA-4 did not alter T cell motility or abrogate tolerance. Thus, PD-1-PD-L1 interactions maintain peripheral tolerance by mechanisms fundamentally distinct from those of CTLA-4...
  18. ncbi request reprint The NOD mouse: a model of immune dysregulation
    Mark S Anderson
    Diabetes Center, University of California, San Francisco, California 94143, USA
    Annu Rev Immunol 23:447-85. 2005
    ..The information gained from this highly relevant model of human disease will lead to potential therapies that may alter the development of the disease and its progression in patients with T1D...
  19. ncbi request reprint Expansion of functional endogenous antigen-specific CD4+CD25+ regulatory T cells from nonobese diabetic mice
    Emma L Masteller
    Diabetes Center, Department of Medicine, University of California, San Francisco, CA 94143 0540, USA
    J Immunol 175:3053-9. 2005
    ..These results provide a direct demonstration of the presence of autoantigen-specific T(reg) in the natural setting that can be applied as therapeutics for organ-specific autoimmunity...
  20. doi request reprint The Immune Tolerance Network at 10 years: tolerance research at the bedside
    Jeffrey A Bluestone
    Diabetes Center and Department of Medicine, University of California, San Francisco, San Francisco, California 94143, USA
    Nat Rev Immunol 10:797-803. 2010
    ..ITN investigators have published more than 80 original research papers based on this work. This Timeline article summarizes the progress and challenges of clinical research in the ITN...
  21. pmc Sequential development of interleukin 2-dependent effector and regulatory T cells in response to endogenous systemic antigen
    Birgit Knoechel
    Department of Pathology, University of California, San Francisco, School of Medicine, CA 94143, USA
    J Exp Med 202:1375-86. 2005
    ..Thus, a peripheral T cell reaction to a systemic antigen goes through a phase of effector cell-mediated pathology followed by T reg cell-mediated recovery, and both require the growth factor IL-2...
  22. pmc Visualizing regulatory T cell control of autoimmune responses in nonobese diabetic mice
    Qizhi Tang
    Diabetes Center, Department of Medicine, University of California, San Francisco 94143, USA
    Nat Immunol 7:83-92. 2006
    ..Such persistent T(reg) cell-dendritic cell contacts preceded the inhibition of T(H) cell activation by dendritic cells, supporting the idea that dendritic cells are central to T(reg) cell function in vivo...
  23. ncbi request reprint Achieving antigen-specific tolerance in diabetes: regulating specifically
    Wei Chen
    Naomi Berrie Diabetes Center and the Division of Endocrinology, Department of Medicine, College of Physicians and Surgeons, Columbia University, New York, NY 10032, USA
    Int Rev Immunol 24:287-305. 2005
    ....
  24. pmc Central role of defective interleukin-2 production in the triggering of islet autoimmune destruction
    Qizhi Tang
    Department of Surgery, University of California, San Francisco, 513 Parnassus Avenue, Box 0540, San Francisco, CA 94143 0540, USA
    Immunity 28:687-97. 2008
    ..Together, these results suggest intra-islet Treg cell dysfunction secondary to defective IL-2 production is a root cause of the progressive breakdown of self-tolerance and the development of diabetes in nonobese diabetic mice...
  25. pmc Spontaneous development of a pancreatic exocrine disease in CD28-deficient NOD mice
    Craig Meagher
    Diabetes Center, University of California, San Francisco, CA 94143, USA
    J Immunol 180:7793-803. 2008
    ..CD28KO mice provides an excellent model for the study of disease pathogenesis and development of new therapies for human autoimmune pancreatitis...
  26. pmc Developing combination immunotherapies for type 1 diabetes: recommendations from the ITN-JDRF Type 1 Diabetes Combination Therapy Assessment Group
    J B Matthews
    Immune Tolerance Network, San Francisco, CA 94107, USA
    Clin Exp Immunol 160:176-84. 2010
    ....
  27. doi request reprint Control of peripheral T-cell tolerance and autoimmunity via the CTLA-4 and PD-1 pathways
    Brian T Fife
    Department of Medicine, UCSF Diabetes Center, University of California, San Francisco, CA 94113, USA
    Immunol Rev 224:166-82. 2008
    ....
  28. pmc T-bet-deficient NOD mice are protected from diabetes due to defects in both T cell and innate immune system function
    Jonathan H Esensten
    Diabetes Center and the Department of Medicine, University of California, San Francisco, 94143, USA
    J Immunol 183:75-82. 2009
    ..Thus, the absence of diabetes in the NOD.Tbx21(-/-) is due to intrinsic defects in both T cells and cells of the innate immune system paired with the relative preservation of regulatory T cell function...
  29. ncbi request reprint Beta-cell replacement for type I diabetes
    Peter G Stock
    Department of Surgery, Division of Transplantation, University of California, San Francisco, San Francisco, California 94143, USA
    Annu Rev Med 55:133-56. 2004
    ..Widespread application of islet transplantation will depend on further improvements in selective immunosuppression, development of immunologic tolerance, and finding new sources of beta cells...
  30. ncbi request reprint CTLA-4 and tolerance: the biochemical point of view
    Shunsuke Chikuma
    Diabetes Center, University of California at San Francisco, San Francisco, CA 94143 0540
    Immunol Res 28:241-53. 2003
    ..A model is proposed based on these observations, which proposes that CTLA-4 may, in fact, function under some circumstances in a ligand-independent manner...
  31. ncbi request reprint Peptide-MHC class II dimers as therapeutics to modulate antigen-specific T cell responses in autoimmune diabetes
    Emma L Masteller
    Diabetes Center, University of California, San Francisco, CA 94143, USA
    J Immunol 171:5587-95. 2003
    ..Anti-IL-10R therapy reversed the tolerogenic effects of the dimer. Thus, peptide I-A(g7) dimers induce tolerance of BDC2.5 TCR T cells through a combination of the induction of clonal anergy and anti-inflammatory cytokines...
  32. ncbi request reprint CD28/B7 regulation of anti-CD3-mediated immunosuppression in vivo
    Qizhi Tang
    Diabetes Center and Department of Medicine, University of California, San Francisco, CA 94143, USA
    J Immunol 170:1510-6. 2003
    ....
  33. pmc TCR stimulation with modified anti-CD3 mAb expands CD8+ T cell population and induces CD8+CD25+ Tregs
    Brygida Bisikirska
    Department of Medicine, College of Physicians and Surgeons, Columbia University, New York, New York 10032, USA
    J Clin Invest 115:2904-13. 2005
    ..Foxp3 was also induced on CD8+ T cells in patients during mAb treatment, which suggests a potential mechanism of the anti-CD3 mAb immune modulatory effects involving induction of a subset of regulatory CD8+ T cells...
  34. ncbi request reprint Distinct effector mechanisms in the development of autoimmune neuropathy versus diabetes in nonobese diabetic mice
    Helene Bour-Jordan
    University of California, San Francisco UCSF Diabetes Center, Department of Medicine, University of California, San Francisco, CA 94143, USA
    J Immunol 175:5649-55. 2005
    ..Thus, there are sharp contrasts in the pathogenesis of autoimmune diseases targeting different tissues in the same NOD background...
  35. pmc Inhibition of T cell activation and autoimmune diabetes using a B cell surface-linked CTLA-4 agonist
    Brian T Fife
    UCSF Diabetes Center, Department of Medicine, UCSF, San Francisco, California 94143, and Department of Internal Medicine, Division of Nephrology, Mayo Clinic, Rochester, Minnesota, USA
    J Clin Invest 116:2252-61. 2006
    ....
  36. pmc Selective miRNA disruption in T reg cells leads to uncontrolled autoimmunity
    Xuyu Zhou
    Diabetes Center, University of California, San Francisco, San Francisco, CA 94143, USA
    J Exp Med 205:1983-91. 2008
    ..These results support a central role for miRNAs in maintaining the stability of differentiated T reg cell function in vivo and homeostasis of the adaptive immune system...
  37. pmc Insulin-induced remission in new-onset NOD mice is maintained by the PD-1-PD-L1 pathway
    Brian T Fife
    UCSF Diabetes Center, Department of Medicine, University of California, San Francisco, San Francisco, CA 94143, and Transplantation Research Center, Brigham and Women s Hospital, Boston, MA 02115, USA
    J Exp Med 203:2737-47. 2006
    ....
  38. ncbi request reprint Sensory neurons link the nervous system and autoimmune diabetes
    Helene Bour-Jordan
    UCSF Diabetes Center, Department of Medicine, University of California, San Francisco, 513 Parnassus Avenue, Box 0540, San Francisco, CA 94143, USA
    Cell 127:1097-9. 2006
    ..In this issue of Cell, propose that a defect in a subset of sensory neurons innervating the pancreas plays a major role in initiating the chain of events that will lead to local inflammation, islet destruction, and autoimmune diabetes...
  39. ncbi request reprint Constitutive expression of B7-1 on B cells uncovers autoimmunity toward the B cell compartment in the nonobese diabetic mouse
    Helene Bour-Jordan
    University of California, San Francisco Diabetes Center, Department of Medicine, CA 94143, USA
    J Immunol 179:1004-12. 2007
    ....
  40. doi request reprint Is antigen specificity of autoreactive T cells the key to islet entry?
    Cristina Penaranda
    Department of Medicine, Diabetes Center, University of California, San Francisco, San Francisco, California 94143, USA
    Immunity 31:534-6. 2009
    ..In this issue of Immunity, Lennon et al. (2009) demonstrate that islet-antigen specificity is required for accumulation in the islets...
  41. pmc Prevention of diabetes by FTY720-mediated stabilization of peri-islet tertiary lymphoid organs
    Cristina Penaranda
    Diabetes Center and Department of Medicine, University of California, San Francisco, San Francisco, California, USA
    Diabetes 59:1461-8. 2010
    ..In this study, we address the role of tertiary lymphoid organs (TLOs) that form in the pancreas of NOD mice during disease progression...
  42. ncbi request reprint The role of CD28 and CTLA4 in the function and homeostasis of CD4+CD25+ regulatory T cells
    Elisa Boden
    UCSF Diabetes Center, University of California, San Francisco, 513 Parnassus Avenue, Box 0540, HSW Room 1114, San Francisco, CA 94143 0540, USA
    Novartis Found Symp 252:55-63; discussion 63-6, 106-14. 2003
    ..Thus, clinical application of co-stimulatory blockade using agents such as CTLA4Ig in the treatment of autoimmune disease may result in complicated outcomes...
  43. ncbi request reprint Distinct roles of CTLA-4 and TGF-beta in CD4+CD25+ regulatory T cell function
    Qizhi Tang
    UCSF Diabetes Center, University of California San Francisco, San Francisco, CA 94143 0540, USA
    Eur J Immunol 34:2996-3005. 2004
    ..These results help explain contradictions in the literature and support the existence of functionally distinct Treg...
  44. ncbi request reprint CD4+CD25+ regulatory T cells in transplantation: progress, challenges and prospects
    S M Kang
    Transplantation Division, Department of Surgery, University of California, San Francisco, CA, USA
    Am J Transplant 7:1457-63. 2007
    ....
  45. ncbi request reprint CD28/B7 costimulation regulates autoimmune diabetes induced with multiple low doses of streptozotocin
    K C Herold
    Department of Medicine, University of Illinois at Chicago, 60612, USA
    J Immunol 158:984-91. 1997
    ..CD80 and CD86 molecules, the CD28/CTLA4 ligands, may have different roles in regulation of the disease and affect T cell function at steps beyond differentiation into mature phenotypes...
  46. pmc Islet transplantation in type 1 diabetics using an immunosuppressive protocol based on the anti-LFA-1 antibody efalizumab
    A M Posselt
    Transplant Surgery, University of California, San Francisco, CA, USA
    Am J Transplant 10:1870-80. 2010
    ..Such an approach may minimize renal and islet toxicity and thus further improve long-term islet allograft survival...
  47. pmc The Immune Tolerance Network: tolerance at the crossroads
    J A Bluestone
    Immune Tolerance Network, University of California, San Francisco, 513 Parnossus Avenue, Box 0540 HSW Room 1114, San Francisco, CA 94143 0540, USA
    Philos Trans R Soc Lond B Biol Sci 356:773-6. 2001
    ..This work has been funded by the National Institutes of Health (in collaboration with the Juvenile Diabetes Foundation International)...
  48. ncbi request reprint Regulation of cytotoxic T lymphocyte-associated molecule-4 by Src kinases
    E Chuang
    Gwen Knapp Center for Lupus and Immunology Research, Department of Medicine, University of Chicago, Chicago, IL 60637, USA
    J Immunol 162:1270-7. 1999
    ..The association of CTLA-4 with Src kinases and with SHP-2 results in the formation of a CTLA-4 complex with the potential to regulate T cell activation...
  49. doi request reprint Human regulatory T cells: role in autoimmune disease and therapeutic opportunities
    Todd M Brusko
    Diabetes Center, University of California, San Francisco, CA 94143 0540, USA
    Immunol Rev 223:371-90. 2008
    ..In summary, the review provides an in-depth analysis and highlights the challenges and opportunities for immune intervention with Treg-based therapeutics...
  50. ncbi request reprint Immunotherapy of insulin-dependent diabetes mellitus
    Emma L Masteller
    UCSF Diabetes Center, Department of Medicine, University of California, San Francisco, CA 94143, USA
    Curr Opin Immunol 14:652-9. 2002
    ..Several of these approaches employing monoclonal antibodies against the TCR-CD3 complex or soluble peptide antigens are producing favorable results in the clinic...
  51. pmc In vitro-expanded antigen-specific regulatory T cells suppress autoimmune diabetes
    Qizhi Tang
    UCSF Diabetes Center, University of California San Francisco, 94143, USA
    J Exp Med 199:1455-65. 2004
    ..Most significantly, small numbers of antigen-specific Tregs can reverse diabetes after disease onset, suggesting a novel approach to cellular immunotherapy for autoimmunity...
  52. pmc B cell depletion: a novel therapy for autoimmune diabetes?
    Helene Bour-Jordan
    Diabetes Center, Department of Medicine, UCSF, San Francisco, California 94143 0540, USA
    J Clin Invest 117:3642-5. 2007
    ..Although many questions remain unanswered, this mouse model represents the first opportunity to evaluate the potential value of rituximab as a novel therapy for autoimmune diabetes...
  53. ncbi request reprint Regulatory T-cell physiology and application to treat autoimmunity
    Qizhi Tang
    UCSF Diabetes Center, Department of Medicine and Department of Pathology, University of California, San Francisco, CA 94143 0540, USA
    Immunol Rev 212:217-37. 2006
    ....
  54. ncbi request reprint The Src family kinase Fyn mediates signals induced by TCR antagonists
    Qizhi Tang
    The Diabetes Center, University of California, San Francisco, CA 94143, USA
    J Immunol 168:4480-7. 2002
    ..Overexpression of Fyn, but not Lck, restored the mitogenicity of FcR nonbinding anti-CD3 in primary T cells. Taken together, these results suggest that Fyn mediates the partial signaling induced by TCR antagonists...
  55. pmc Loss of integrin alpha(v)beta8 on dendritic cells causes autoimmunity and colitis in mice
    Mark A Travis
    Lung Biology Center, Department of Medicine, University of California San Francisco, 1550 4th Street, Room 545, San Francisco, California 94158, USA
    Nature 449:361-5. 2007
    ....
  56. pmc A novel myelin P0-specific T cell receptor transgenic mouse develops a fulminant autoimmune peripheral neuropathy
    Cedric Louvet
    Diabetes Center and the Department of Medicine, University of California, San Francisco, San Francisco, CA 94143, USA
    J Exp Med 206:507-14. 2009
    ..Collectively, our data suggest that myelin P0 is a major autoantigen in autoimmune peripheral neuropathy...
  57. ncbi request reprint CTLA-4 regulates the requirement for cytokine-induced signals in T(H)2 lineage commitment
    Helene Bour-Jordan
    UCSF Diabetes Center and Department of Medicine, University of California San Francisco, 94143, USA
    Nat Immunol 4:182-8. 2003
    ..These results suggest that CTLA-4 has a critical role in T cell differentiation and that STAT6-dependent T(H)2 lineage commitment and stabilization can be bypassed by increasing the strength of signaling through the T cell receptor...
  58. ncbi request reprint Impairment of NK cell function by NKG2D modulation in NOD mice
    Kouetsu Ogasawara
    Department of Microbiology and Immunology, University of California San Francisco, 513 Parnassus Avenue HSE 420, Box 0414, San Francisco, CA 94143, USA
    Immunity 18:41-51. 2003
    ..Modulation of NKG2D was mostly dependent on the YxxM motif of DAP10, the NKG2D-associated adaptor that activates phosphoinositide 3 kinase. These results suggest that NK cells may be desensitized by exposure to NKG2D ligands...
  59. ncbi request reprint Regulation of C-C chemokine production by murine T cells by CD28/B7 costimulation
    K C Herold
    Department of Medicine, The University of Illinois at Chicago, 60612, USA
    J Immunol 159:4150-3. 1997
    ..Thus, CD28 costimulation may amplify an immune response by stimulating T cell survival, proliferation, and production of chemokines that recruit T cells to inflammatory sites...
  60. pmc Regulatory T cells as therapeutic targets in rheumatoid arthritis
    Jonathan H Esensten
    Diabetes Center, University of California, San Francisco, San Francisco, CA 94143, USA
    Nat Rev Rheumatol 5:560-5. 2009
    ..Thus, cell-based therapy with TREG has the potential to produce durable disease remission in patients with RA...
  61. pmc Plasticity of CD4(+) FoxP3(+) T cells
    Xuyu Zhou
    Diabetes Center and the Department of Medicine, University of California, San Francisco, CA 94143, USA
    Curr Opin Immunol 21:281-5. 2009
    ..The presence of these 'exTregs' in multiple inflammatory settings suggests a potential role for these cells in a variety of disease settings ranging from autoimmunity to cancer and infectious disease...
  62. pmc Instability of the transcription factor Foxp3 leads to the generation of pathogenic memory T cells in vivo
    Xuyu Zhou
    Diabetes Center and the Department of Medicine, University of California, San Francisco, California, USA
    Nat Immunol 10:1000-7. 2009
    ..Thus, the generation of potentially autoreactive effector T cells as a consequence of Foxp3 instability has important implications for understanding autoimmune disease pathogenesis...
  63. ncbi request reprint Inability to induce tolerance through direct antigen presentation
    Ingrid C Rulifson
    UCSF Diabetes Center, University of California, San Francisco 94143 0540, USA
    Am J Transplant 2:510-9. 2002
    ....
  64. pmc Regulating the regulators: costimulatory signals control the homeostasis and function of regulatory T cells
    Helene Bour-Jordan
    UCSF Diabetes Center, University of California at San Francisco, San Francisco, CA, USA
    Immunol Rev 229:41-66. 2009
    ..In this review, we discuss the connections between costimulation and Tregs that have changed the costimulation paradigm...
  65. pmc Expansion of human regulatory T-cells from patients with type 1 diabetes
    Amy L Putnam
    Diabetes Center at the University of California, San Francisco UCSF, San Francisco, California, USA
    Diabetes 58:652-62. 2009
    ..However, translating Treg-based therapies from animal models of autoimmunity to human clinical trials requires robust methods for the isolation and expansion of these cells-a need forming the basis for these studies...
  66. doi request reprint Small RNA regulators of T cell-mediated autoimmunity
    Lukas T Jeker
    Diabetes Center and the Department of Medicine, University of California, San Francisco, San Francisco, CA 94143, USA
    J Clin Immunol 30:347-57. 2010
    ..MicroRNAs (miRNAs) are short singlestranded RNA molecules that regulate gene expression post-transcriptionally. Several hundred miRNAs exist in the mammalian genome and regulate developmental processes, cell cycle, and survival...
  67. pmc The role of X-linked FOXP3 in the autoimmune susceptibility of Turner Syndrome patients
    Maureen A Su
    Department of Pediatrics, University of California, San Francisco, CA 94143, USA
    Clin Immunol 131:139-44. 2009
    ..These findings suggest that the autoimmune predisposition in Turner Syndrome is not due to alterations in regulatory T cells but may be associated with a change in the proportion of T cell subsets...
  68. pmc Tyrosine kinase inhibitors reverse type 1 diabetes in nonobese diabetic mice
    Cedric Louvet
    Diabetes Center and the Department of Medicine, University of California, San Francisco, CA 94143, USA
    Proc Natl Acad Sci U S A 105:18895-900. 2008
    ..Thus, long-term efficacy and tolerance is likely to depend on inhibiting a combination of tyrosine kinases supporting the use of selective kinase inhibitors as a new, potentially very attractive approach for the treatment of T1D...
  69. pmc Negative regulation of T cell receptor-lipid raft interaction by cytotoxic T lymphocyte-associated antigen 4
    Shunsuke Chikuma
    Diabetes Center, University of California at San Francisco, San Francisco, CA 94143, USA
    J Exp Med 197:129-35. 2003
    ..These results suggest that CTLA-4 functions to regulate T cell signaling by controlling TCR accumulation and/or retention within this a critical component of the immunological synapse...
  70. pmc CD127 expression inversely correlates with FoxP3 and suppressive function of human CD4+ T reg cells
    Weihong Liu
    UCSF Diabetes Center, Department of Medicine, University of California, San Francisco, San Francisco, CA 94143, USA
    J Exp Med 203:1701-11. 2006
    ..Finally, we show that CD127 can be used to quantitate T reg cell subsets in individuals with type 1 diabetes supporting the use of CD127 as a biomarker for human T reg cells...
  71. ncbi request reprint CTLA4Ig: bridging the basic immunology with clinical application
    Jeffrey A Bluestone
    Diabetes Center, University of California, San Francisco, San Francisco, California 94143, USA
    Immunity 24:233-8. 2006
    ..Orencia is the first-in-class antagonist of CD28 costimulation. In this perspective, we discuss the science that led to CTLA4Ig development and the clinical challenges in bringing the drug from the bench to the bedside...
  72. ncbi request reprint NKG2D blockade prevents autoimmune diabetes in NOD mice
    Kouetsu Ogasawara
    Department of Microbiology and Immunology and the Cancer Research Institute, HSE 1001, Box 0414, University of California, San Francisco, 513 Parnassus Avenue, San Francisco, CA 94143, USA
    Immunity 20:757-67. 2004
    ..These findings demonstrate that NKG2D is essential for disease progression and suggest a new therapeutic target for autoimmune type I diabetes...
  73. ncbi request reprint Notch 1 signaling regulates peripheral T cell activation
    Todd N Eagar
    Diabetes Center and Department of Medicine, University of California, San Francisco, San Francisco, CA 94143 USA
    Immunity 20:407-15. 2004
    ..Similar effects were observed in vivo in an adoptive transfer model. Therefore, Notch 1 signaling may play an important role in regulating naive T cell activation and homeostasis...
  74. ncbi request reprint B7-independent inhibition of T cells by CTLA-4
    Shunsuke Chikuma
    University of California at San Francisco Diabetes Center and Department of Medicine, University of California, San Francisco, CA 94143, USA
    J Immunol 175:177-81. 2005
    ..These results suggest that ligand binding is not essential for the CTLA-4 function and supports an essential role for CTLA-4 signaling during T cell activation...
  75. ncbi request reprint Expression of CTLA-4 and FOXP3 in cis protects from lethal lymphoproliferative disease
    Shunsuke Chikuma
    UCSF Diabetes Center, Department of Medicine, University of California, San Francisco, CA 94143 0450, USA
    Eur J Immunol 37:1285-9. 2007
    ..These results suggest common attributes of both diseases, but expression of both CTLA-4 and FoxP3 on the same cell subset is essential to fully prevent LP disease...
  76. ncbi request reprint A comprehensive review of interventions in the NOD mouse and implications for translation
    Lisl K M Shoda
    Entelos Inc, Foster City, California 94404, USA
    Immunity 23:115-26. 2005
    ....
  77. ncbi request reprint TGF-beta-dependent mechanisms mediate restoration of self-tolerance induced by antibodies to CD3 in overt autoimmune diabetes
    Meriam Belghith
    INSERM U580, IRNEM, Hopital Necker, 161 rue de Sevres, 75015 Paris, France
    Nat Med 9:1202-8. 2003
    ..These data explain the intriguing tolerogenic effect of CD3-specific antibodies and position them as the first clinically applicable pharmacological stimulant of TGF-beta-producing regulatory CD4+ T cells...
  78. ncbi request reprint The role of CTLA-4 in induction and maintenance of peripheral T cell tolerance
    Todd N Eagar
    Department of Microbiology Immunology and Interdepartmental Immunobiology Center, Northwestern University Medical School, Chicago, IL 60611, USA
    Eur J Immunol 32:972-81. 2002
    ....
  79. pmc Activation of human T cells by FcR nonbinding anti-CD3 mAb, hOKT3gamma1(Ala-Ala)
    Kevan C Herold
    Naomi Berrie Diabetes Center, Department of Medicine and Division of Endocrinology, College of Physicians and Surgeons, Columbia University, New York, New York 10032, USA
    J Clin Invest 111:409-18. 2003
    ..It leads to the generation of T cells that might inhibit the autoimmune response and may be involved in the beneficial effect on beta cell destruction in Type 1 diabetes...
  80. ncbi request reprint Distinct roles of dendritic cells and B cells in Va14Ja18 natural T cell activation in vivo
    Jelena S Bezbradica
    Department of Microbiology and Immunology, Vanderbilt University School of Medicine, Nashville, TN 37232, USA
    J Immunol 174:4696-705. 2005
    ..Thus, the differential immune outcome based on the type of APC that displays glycolipid Ags in vivo has implications for the design of therapies that harness the immunoregulatory functions of iNKT cells...
  81. ncbi request reprint Treatment with nonmitogenic anti-CD3 monoclonal antibody induces CD4+ T cell unresponsiveness and functional reversal of established experimental autoimmune encephalomyelitis
    Adam P Kohm
    Department of Microbiology Immunology and Interdepartmental Immunobiology Center, Northwestern University Medical School, Chicago, IL 60611, USA
    J Immunol 174:4525-34. 2005
    ....
  82. ncbi request reprint Peptide specific amelioration of T cell mediated pathogenesis in murine type 1 diabetes
    Valeria Judkowski
    Torrey Pines Institute for Molecular Studies, San Diego, CA 92121, USA
    Clin Immunol 113:29-37. 2004
    ..5 T cells results in protection from disease. These results suggest that high affinity peptide analogues of autoimmune epitopes might be useful as therapeutic modulators in active autoimmune disease...
  83. ncbi request reprint CTLA-4 regulates expansion and differentiation of Th1 cells following induction of peripheral T cell tolerance
    Todd N Eagar
    Department of Microbiology Immunology and Interdepartmental Immunobiology Center, Northwestern University Medical School, 303 East Chicago Avenue, Chicago, IL 60611, USA
    J Immunol 172:7442-50. 2004
    ..This unresponsiveness was reversible by treatment with anti-CTLA-4 mAb. These results are consistent with the hypothesis that Ag-SP injection induces a state of T cell anergy that is maintained by CTLA-4 engagement...
  84. ncbi request reprint A peptide of glutamic acid decarboxylase 65 can recruit and expand a diabetogenic T cell clone, BDC2.5, in the pancreas
    Yang D Dai
    Division of Immune Regulation, Torrey Pines Institute for Molecular Studies, San Diego, CA 92121, USA
    J Immunol 175:3621-7. 2005
    ..5 cells in the pancreas has been observed, presumably due to tolerance induction. These data suggest that unique and/or altered processing of self Ags may play an essential role in the development and expansion of autoreactive T cells...
  85. ncbi request reprint Transplantation of cultured islets from two-layer preserved pancreases in type 1 diabetes with anti-CD3 antibody
    Bernhard J Hering
    Diabetes Institute for Immunology and Transplantation, Department of Surgery, University of Minnesota, Minneapolis, MN, USA
    Am J Transplant 4:390-401. 2004
    ..Our preliminary results thus suggest that a combination of maximized viable islet yield, pretransplant islet culture, and preemptive immunosuppression can result in successful single-donor islet transplants...
  86. ncbi request reprint When ligand becomes receptor--tolerance via B7 signaling on DCs
    Erik B Finger
    Nat Immunol 3:1056-7. 2002
  87. ncbi request reprint Exendin-4 improves reversal of diabetes in NOD mice treated with anti-CD3 monoclonal antibody by enhancing recovery of beta-cells
    Nicole A Sherry
    Department of Immunobiology, Yale University, New Haven, CT 06520, USA
    Endocrinology 148:5136-44. 2007
    ..This combinatorial approach may be useful in treatment of patients with new-onset T1DM...
  88. ncbi request reprint Cutting edge: targeted ligation of CTLA-4 in vivo by membrane-bound anti-CTLA-4 antibody prevents rejection of allogeneic cells
    Kwang Woo Hwang
    Department of Medicine and Committee in Immunology, University of Chicago, Chicago, IL 60637, USA
    J Immunol 169:633-7. 2002
    ..Furthermore, CTLA-4(+/+) T cells that had encountered 7M-expressing tumors in vivo acquired defects in cytokine production and cytotoxicity. Thus, deliberate ligation of CTLA-4 in vivo potently inhibits allogeneic T cell responses...
  89. ncbi request reprint Mechanisms of PDL1-mediated regulation of autoimmune diabetes
    Indira Guleria
    Transplantation Research Center, Brigham and Women s Hospital and Children s Hospital Boston, Harvard Medical School, Boston, MA 02115, USA
    Clin Immunol 125:16-25. 2007
    ..These data provide strong evidence that PDL1 regulates autoimmune diabetes by limiting the expansion of CD4+ and CD8+ autoreactive T cells, and define the timing and locale of PDL1-mediated regulation of type 1 diabetes...
  90. pmc Adaptive TGF-beta-dependent regulatory T cells control autoimmune diabetes and are a privileged target of anti-CD3 antibody treatment
    Sylvaine You
    Universite Paris Descartes, 75015 Paris, France
    Proc Natl Acad Sci U S A 104:6335-40. 2007
    ....
  91. ncbi request reprint CD3-specific antibodies: a portal to the treatment of autoimmunity
    Lucienne Chatenoud
    Universite Rene Descartes, Paris 5, Institut National de la Sante et de la Recherche Medicale, Unité 580, Hopital Necker Enfants Malades, 161 rue de Sèvres 75743 Paris CEDEX 15, France
    Nat Rev Immunol 7:622-32. 2007
    ..This Review summarizes the pre-clinical and clinical studies of CD3-specific monoclonal antibody therapy and highlights future opportunities to enhance the efficacy of this potent immunotherapeutic...
  92. doi request reprint CD3-specific antibody-induced immune tolerance involves transforming growth factor-beta from phagocytes digesting apoptotic T cells
    Sylvain Perruche
    Mucosal Immunology Unit, Oral Infection and Immunity Branch, National Institute of Dental and Craniofacial Research NIDCR, US National Institutes of Health NIH, 30 Convent Drive, Bethesda, Maryland 20892, USA
    Nat Med 14:528-35. 2008
    ..Thus, CD3-specific antibody-induced immune tolerance is associated with TGF-beta production in phagocytes involved in clearing apoptotic T cells, which suggests that apoptosis is linked to active suppression in immune tolerance...
  93. ncbi request reprint Anti-CD3 monoclonal antibody in new-onset type 1 diabetes mellitus
    Kevan C Herold
    Naomi Berrie Diabetes Center and the Department of Medicine, Division of Endocrinology, College of Physicians and Surgeons, Columbia University, New York 10032, USA
    N Engl J Med 346:1692-8. 2002
    ..Preclinical studies suggested that a monoclonal antibody against CD3 could reverse hyperglycemia at presentation and induce tolerance to recurrent disease...
  94. ncbi request reprint The immune tolerance network: a new paradigm for developing tolerance-inducing therapies
    Daniel Rotrosen
    National Institute of Allergy and Infectious Diseases, Bethesda, MD 20817, USA
    J Allergy Clin Immunol 110:17-23. 2002
    ..This report summarizes the rationale for emphasizing clinical research on immune tolerance and highlights the progress of the ITN...
  95. ncbi request reprint An important role of CD80/CD86-CTLA-4 signaling during photocarcinogenesis in mice
    Karin Loser
    Department of Dermatology, University of Munster, Munster, Germany
    J Immunol 174:5298-305. 2005
    ..Furthermore, CD86-mediated costimulation appears to play a more critical role in the protection against photocarcinogenesis than CD80...
  96. ncbi request reprint Analysis of T-cell assays to measure autoimmune responses in subjects with type 1 diabetes: results of a blinded controlled study
    Vicki Seyfert-Margolis
    Immune Teolerance Network, Bethesda, Maryland, USA
    Diabetes 55:2588-94. 2006
    ..They may be useful for assessment of cellular autoimmune responses involved in type 1 diabetes...
  97. pmc Innate immunity and intestinal microbiota in the development of Type 1 diabetes
    Li Wen
    Section of Endocrinology, Yale University School of Medicine, New Haven, Connecticut 06520, USA
    Nature 455:1109-13. 2008
    ..Together, these findings indicate that interaction of the intestinal microbes with the innate immune system is a critical epigenetic factor modifying T1D predisposition...
  98. ncbi request reprint Plasmacytoid DCs and T(reg) cells: casual acquaintance or monogamous relationship?
    Qizhi Tang
    Nat Immunol 7:551-3. 2006
  99. ncbi request reprint What does the future hold for cell-based tolerogenic therapy?
    Jeffrey A Bluestone
    Immune Tolerance Network and of the Diabetes Center at the University of California, USA
    Nat Rev Immunol 7:650-4. 2007
    ....

Research Grants4

  1. Conf on Mechanism and Applications of Immune Tolerance
    Jeffrey Bluestone; Fiscal Year: 2002
    ..Finally, specific talks in immunotherapy of autoimmunity, transplantation, cancer and infectious disease will be included. ..
  2. Role of Notch 1 in Immune Tolerance
    Jeffrey Bluestone; Fiscal Year: 2005
    ..To Identify the biochemical, cellular and genetic effects of Notch signaling in T cells; and Specific Aim #2. In vivo application of Notch signaling for the establishment of peripheral T cell tolerance. ..
  3. IMMUNOMODULATION OF TRANSPLANT REJECTION BY ANTI-CD3 MAB
    Jeffrey Bluestone; Fiscal Year: 2007
    ..3) Use biochemical analyses and retroviral gene transfer to define the distal signaling events associated with clonal inactivation, cell death, and T helper subset differentiation induced by 2C11-IgG3. ..