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 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
  4. 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
  5. 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
  6. 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
  7. 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
  8. 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
  9. 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
  10. 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

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

Collaborators

Detail Information

Publications133 found, 100 shown here

  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 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...
  4. 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...
  5. 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...
  6. 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...
  7. 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...
  8. 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
    ....
  9. 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...
  10. 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...
  11. 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...
  12. 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...
  13. 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...
  14. 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...
  15. 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
    ....
  16. 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...
  17. 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...
  18. 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...
  19. ncbi request reprint Complexities of CD28/B7: CTLA-4 costimulatory pathways in autoimmunity and transplantation
    B Salomon
    The Committee on Immunology, Ben May Institute for Cancer Research and Department of Pathology, University of Chicago, Chicago, Illinois 60637, USA
    Annu Rev Immunol 19:225-52. 2001
    ..The implications of these complexities and the potential for use of these therapies in clinical immune intervention are discussed...
  20. ncbi request reprint B7/CD28 costimulation is essential for the homeostasis of the CD4+CD25+ immunoregulatory T cells that control autoimmune diabetes
    B Salomon
    Committee on Immunology, Ben May Institute for Cancer Research and Department of Pathology, University of Chicago, Illinois 60637, USA
    Immunity 12:431-40. 2000
    ..The results suggest that the CD28/ B7 costimulatory pathway is essential for the development and homeostasis of regulatory T cells that control spontaneous autoimmune diseases...
  21. ncbi request reprint Different mechanisms of cardiac allograft rejection in wildtype and CD28-deficient mice
    G L Szot
    Ben May Institute for Cancer Research, The University of Chicago, IL 60637, USA
    Am J Transplant 1:38-46. 2001
    ..These results may help to explain the failure to promote graft tolerance in some preclinical and clinical settings...
  22. ncbi request reprint Cutting edge: blockade of the CD28/B7 costimulatory pathway inhibits intestinal allograft rejection mediated by CD4+ but not CD8+ T cells
    K A Newell
    Department of Surgery, Committee on Immunology, Ben May Institute for Cancer Research, University of Chicago, IL 60637, USA
    J Immunol 163:2358-62. 1999
    ..The results also suggest that the inhibition of CD4+ T cell-mediated allograft rejection by CTLA4Ig may be related to down-regulation of Th1 cytokines and/or up-regulation of Th2 cytokines...
  23. ncbi request reprint Lymphoproliferative disorder in CTLA-4 knockout mice is characterized by CD28-regulated activation of Th2 responses
    R Khattri
    Committee on Immunology, Ben May Institute for Cancer Research, Department of Pathology, University of Chicago, Chicago, IL 60637, USA
    J Immunol 162:5784-91. 1999
    ..Thus, CTLA-4 regulates CD28-dependent peripheral activation of CD4+ T cells. This process results in apoptosis-resistant, CD4+ T cells with a predominantly Th2 phenotype that may be involved in the lethal phenotype in these animals...
  24. 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...
  25. ncbi request reprint A critical role for B7/CD28 costimulation in experimental autoimmune encephalomyelitis: a comparative study using costimulatory molecule-deficient mice and monoclonal antibody blockade
    A M Girvin
    Department of Microbiology Immunology, Northwestern University Medical School, Northwestern University Institute for Neuroscience, Chicago, IL 60611, USA
    J Immunol 164:136-43. 2000
    ..Collectively, these results support a critical role for CD28 costimulation in EAE induction...
  26. 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...
  27. ncbi request reprint CD28 expression is not essential for positive and negative selection of thymocytes or peripheral T cell tolerance
    T L Walunas
    Ben May Institute, University of Chicago, IL 60637, USA
    J Immunol 156:1006-13. 1996
    ..Therefore, it appears that CD28, although not essential for the selection of T cells during development, may allow for additional signals that increase the efficiency of selection and/or expansion of peripheral T cell populations...
  28. ncbi request reprint CD28 costimulation promotes the production of Th2 cytokines
    I C Rulifson
    Ben May Institute for Cancer Research, Department of Pathology, University of Chicago, IL 60637, USA
    J Immunol 158:658-65. 1997
    ..Therefore, CD28 ligation promotes the production of Th2-type cytokines by naive murine T cells via an IL-4-dependent mechanism...
  29. ncbi request reprint CD28/B7 regulation of Th1 and Th2 subsets in the development of autoimmune diabetes
    D J Lenschow
    Ben May Institute for Cancer Research, Department of Pathology, University of Chicago, Illinois 60637, USA
    Immunity 5:285-93. 1996
    ....
  30. ncbi request reprint Anergic T lymphocytes selectively express an integrin regulatory protein of the cytohesin family
    U Korthauer
    Ben May Institute for Cancer Research, University of Chicago, IL 60637, USA
    J Immunol 164:308-18. 2000
    ..However, GRP1-transduced T cells were not stable and rapidly lost GRP1 expression. Thus, although GRP1 may not directly mediate T cell anergy, it regulates cell expansion and survival, perhaps through its integrin-associated activities...
  31. ncbi request reprint Differential up-regulation of the B7-1 and B7-2 costimulatory molecules after Ig receptor engagement by antigen
    D J Lenschow
    Committee on Immunology, University of Chicago, IL 60637
    J Immunol 153:1990-7. 1994
    ..Thus, the effectiveness of Ag-specific B cells as APCs depends on both their enhanced Ag uptake, mediated by the B cell receptor, and immediate up-regulation of a potent costimulatory molecule, B7-2...
  32. pmc CD43 is a murine T cell costimulatory receptor that functions independently of CD28
    A I Sperling
    Ben May Institute, University of Chicago, Chicago, Illinois 60637, USA
    J Exp Med 182:139-46. 1995
    ..Expression cloning of the R2/60 antigen identified the ligand as murine CD43. Together, these data demonstrate that CD43 can serve as a receptor on T cells that can provide CD28-independent costimulation...
  33. ncbi request reprint Development and applications of surface-linked single chain antibodies against T-cell antigens
    M D Griffin
    The Ben May Institute for Cancer Research, Dept. of Pathology and Committee on Immunology, University of Chicago, Chicago, IL, USA
    J Immunol Methods 248:77-90. 2001
    ..Finally, the use of random mutagenesis and yeast surface display to increase the affinity and functional efficacy of scFv constructs is demonstrated...
  34. pmc Antigenic cancer cells grow progressively in immune hosts without evidence for T cell exhaustion or systemic anergy
    M Wick
    Department of Pathology, The University of Chicago, Chicago, Illinois 60637, USA
    J Exp Med 186:229-38. 1997
    ..Thus, the failure of established tumors to attract and activate tumor-specific T cells at the tumor site may be a major obstacle for preventive or therapeutic vaccination against antigenic cancer...
  35. ncbi request reprint CD28 interactions with either CD80 or CD86 are sufficient to induce allergic airway inflammation in mice
    M Mathur
    Department of Pediatrics, The Ben May Institute for Cancer Research, Chicago, Illinois, USA
    Am J Respir Cell Mol Biol 21:498-509. 1999
    ....
  36. 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...
  37. ncbi request reprint Blockade of T cell activation using a surface-linked single-chain antibody to CTLA-4 (CD152)
    M D Griffin
    The Ben May Institute for Cancer Research and Department of Pathology and Committee on Immunology, University of Chicago, Chicago, IL 60637, USA
    J Immunol 164:4433-42. 2000
    ....
  38. 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...
  39. ncbi request reprint Antigen-specific blockade of T cells in vivo using dimeric MHC peptide
    S M O'Herrin
    The Ben May Institute for Cancer Research, Department of Pathology, University of Chicago, Chicago, IL 60637, USA
    J Immunol 167:2555-60. 2001
    ..The prolonged Ag-specific suppression of expansion and/or effector function of cognate T cells in vivo suggests that soluble MHC dimers may be a means of inducing sustained Ag-specific T cell unresponsiveness in vivo...
  40. 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...
  41. ncbi request reprint Loss of CTLA-4 leads to massive lymphoproliferation and fatal multiorgan tissue destruction, revealing a critical negative regulatory role of CTLA-4
    E A Tivol
    Department of Pathology, Brigham and Women s Hospital, Boston, Massachusetts, USA
    Immunity 3:541-7. 1995
    ..In the absence of CTLA-4, peripheral T cells are activated, can spontaneously proliferate, and may mediate lethal tissue injury...
  42. ncbi request reprint IL-4 treatment of small splenic B cells induces costimulatory molecules B7-1 and B7-2
    R M Stack
    Committee on Developmental Biology, University of Chicago, IL 60637
    J Immunol 152:5723-33. 1994
    ..Additionally, these findings support our previous findings that an alternative ligand for CD28 and CTLA4 is important in providing costimulation...
  43. ncbi request reprint Absence of B7-dependent responses in CD28-deficient mice
    J M Green
    Department of Medicine, University of Chicago, Illinois 60637
    Immunity 1:501-8. 1994
    ..Furthermore, our data suggest that CD28 is the primary, and perhaps exclusive, costimulatory receptor used by traditional antigen-presenting cells to augment the proliferation of antigen-activated T cells...
  44. 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...
  45. ncbi request reprint Repertoire development and ligand specificity of murine TCR gamma delta cells
    J A Bluestone
    Department of Pathology, University of Chicago, IL 60637
    Immunol Rev 120:5-33. 1991
    ..In summary, these studies provides a basis for understanding and determining the ligand(s) of the TCR gamma delta heterodimer and the factors which shape the peripheral TCR gamma delta repertoire...
  46. pmc RIBP, a novel Rlk/Txk- and itk-binding adaptor protein that regulates T cell activation
    K Rajagopal
    Committee on Immunology, University of Chicago, Chicago, Illinois 60637, USA
    J Exp Med 190:1657-68. 1999
    ..These data suggest that RIBP plays an important role in TCR-mediated signal transduction pathways and that its binding to Itk and Rlk/Txk may regulate T cell differentiation...
  47. ncbi request reprint Clinical grade manufacturing of human alloantigen-reactive regulatory T cells for use in transplantation
    A L Putnam
    UCSF Diabetes Center, University of California, San Francisco, San Francisco, CA
    Am J Transplant 13:3010-20. 2013
    ..The alloantigen-expanded Tregs had a diverse TCR repertoire. They were more potent than PolyTregs in vitro and more effective at controlling allograft injuries in vivo in a humanized mouse model. ..
  48. ncbi request reprint CD28/B7 system of T cell costimulation
    D J Lenschow
    Committee on Immunology, Ben May Institute, Chicago, Illinois 60637, USA
    Annu Rev Immunol 14:233-58. 1996
    ..It is our hope and expectation that this review will provoke additional research that will unravel this important, yet complex, signaling pathway...
  49. ncbi request reprint Severe combined immunodeficient mice engrafted with human splenocytes have functional human T cells and reject human allografts
    M L Alegre
    Ben May Institute, Department of Pathology, Pritzker School of Medicine, University of Chicago, IL 60637
    J Immunol 153:2738-49. 1994
    ..Thus, this hu-Spl-SCID model may be useful for the study of immunosuppressive therapies in a preclinical in vivo setting...
  50. pmc CD28 costimulatory blockade exacerbates disease severity and accelerates epitope spreading in a virus-induced autoimmune disease
    K L Neville
    Department of Microbiology Immunology, Interdepartmental Immunobiology Center, Northwestern University Medical School, Chicago, Illinois 60611, USA
    J Virol 74:8349-57. 2000
    ..Our results raise concern about the potential use of B7-CD28 costimulatory blockade to treat human autoimmune diseases potentially associated with acute or persistent virus infections...
  51. ncbi request reprint Is CTLA-4 a master switch for peripheral T cell tolerance?
    J A Bluestone
    Ben May Institute for Cancer Research, Committee on Immunology, University of Chicago, IL 60615, USA
    J Immunol 158:1989-93. 1997
    ....
  52. ncbi request reprint Phase I trial of a humanized, Fc receptor nonbinding OKT3 antibody, huOKT3gamma1(Ala-Ala) in the treatment of acute renal allograft rejection
    E S Woodle
    Department of Surgery, Committee on Immunology, Ben May Institute for Cancer Research, University of Chicago, Illinois 60637, USA
    Transplantation 68:608-16. 1999
    ..This report describes the results of a phase I trial of huOKT3gamma1(Ala-Ala) treatment of acute renal allograft rejection...
  53. pmc Reversal of spontaneous autoimmune insulitis in nonobese diabetic mice by soluble lymphotoxin receptor
    Q Wu
    Committee on Immunology and the Department of Pathology, University of Chicago, Chicago, IL 60637, USA
    J Exp Med 193:1327-32. 2001
    ..Thus, LTbetaR-Ig can disassemble the well established lymphoid microenvironment in the islets, which is required for the development and progression of IDDM...
  54. pmc T cell receptor-gamma/delta cells protect mice from herpes simplex virus type 1-induced lethal encephalitis
    R Sciammas
    Ben May Institute for Cancer Research, Department of Pathology and Committee on Immunology, University of Chicago, Chicago, Illinois 60637, USA
    J Exp Med 185:1969-75. 1997
    ..Thus, this study demonstrates that TCR-gamma/delta cells may play an important regulatory role in human HSV-1 infections...
  55. 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
    ....
  56. 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...
  57. 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...
  58. ncbi request reprint Signal transduction through class I MHC by a monoclonal antibody that detects multiple murine and human class I molecules
    B A Houlden
    Committee on Immunology, University of Chicago, Ben May Institute, IL 60637
    J Immunol 146:425-30. 1991
    ..Although class I molecules are not usually considered as activation Ag, these data demonstrate their potential for involvement in signal transduction...
  59. ncbi request reprint CD28/B7 interactions deliver a unique signal to naive T cells that regulates cell survival but not early proliferation
    A I Sperling
    Ben May Institute, University of Chicago, IL 60637, USA
    J Immunol 157:3909-17. 1996
    ..Together, these results suggest that the unique role of CD28 signaling is not to costimulate the initial activation of naive T cells, but is, in fact, to sustain the late proliferative response and enhance long term cell survival...
  60. 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...
  61. 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...
  62. 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...
  63. 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
    ....
  64. 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...
  65. 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...
  66. 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
    ....
  67. 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
    ....
  68. 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...
  69. 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...
  70. 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...
  71. 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...
  72. 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...
  73. 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...
  74. ncbi request reprint Phenotypic and functional analysis of murine CD3+,CD4-,CD8- TCR-gamma delta-expressing peripheral T cells
    R Q Cron
    University of Chicago, Ben May Institute, Department of Pathology, IL 60637
    J Immunol 142:3754-62. 1989
    ..Finally, activated CD3+, CD4-,CD8-,TCR-gamma delta+ splenocytes were also capable of producing IL-2, IL-3, IFN-gamma, and TNF when stimulated in vitro with anti-CD3-epsilon mAb...
  75. 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...
  76. 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...
  77. 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)...
  78. 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...
  79. 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
    ....
  80. 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...
  81. 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...
  82. 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
    ....
  83. ncbi 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...
  84. 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...
  85. 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...
  86. 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
    ....
  87. 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
    ....
  88. 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...
  89. 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
    ....
  90. 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...
  91. 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...
  92. 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...
  93. 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...
  94. 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...
  95. pmc CTLA-4 ligation blocks CD28-dependent T cell activation
    T L Walunas
    Department of Pathology, Ben May Institute for Cancer Research, University of Chicago, Illinois 60637, USA
    J Exp Med 183:2541-50. 1996
    ..These results suggest that CTLA-4 signaling does not regulate cell survival or responsiveness to IL-2, but does inhibit CD28-dependent IL-2 production...
  96. 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...
  97. ncbi 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...
  98. 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...
  99. 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...
  100. 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...
  101. 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...

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. ..