PD 1

Summary

Gene Symbol: PD 1
Description: programmed cell death 1
Alias: Ly101, PD-1, Pdc1, programmed cell death protein 1, mPD-1, programmed cell death 1 protein, protein PD-1
Species: mouse

Top Publications

  1. ncbi PD-1 expression on HIV-specific T cells is associated with T-cell exhaustion and disease progression
    Cheryl L Day
    HIV Pathogenesis Programme, Doris Duke Medical Research Institute, University of KwaZulu Natal, Durban 4013, South Africa
    Nature 443:350-4. 2006
  2. ncbi Development of lupus-like autoimmune diseases by disruption of the PD-1 gene encoding an ITIM motif-carrying immunoreceptor
    H Nishimura
    Department of Medical Chemistry, Faculty of Medicine, Kyoto University, Japan
    Immunity 11:141-51. 1999
  3. ncbi Expression of programmed death 1 ligands by murine T cells and APC
    Tomohide Yamazaki
    Department of Immunology, Juntendo University School of Medicine, 2 1 1 Hongo, Bunkyo ku, Tokyo 113 8421, Japan
    J Immunol 169:5538-45. 2002
  4. pmc PD-1 and LAG-3 inhibitory co-receptors act synergistically to prevent autoimmunity in mice
    Taku Okazaki
    Division of Immune Regulation, Institute for Genome Research, University of Tokushima, Kuramoto, Tokushima, Japan
    J Exp Med 208:395-407. 2011
  5. ncbi PD-1 and PD-1 ligands: from discovery to clinical application
    Taku Okazaki
    21st Century Center of Excellence Formation, Graduate School of Medicine, Kyoto University, Yoshida Konoe, Sakyo ku, Kyoto 606 8501, Japan
    Int Immunol 19:813-24. 2007
  6. pmc Coexpression of Tim-3 and PD-1 identifies a CD8+ T-cell exhaustion phenotype in mice with disseminated acute myelogenous leukemia
    Qing Zhou
    Masonic Cancer Center and Department of Pediatrics, Division of Hematology Oncology and Blood and Marrow Transplantation, Kagawa University, Kagawa, Japan
    Blood 117:4501-10. 2011
  7. pmc Allograft rejection is restrained by short-lived TIM-3+PD-1+Foxp3+ Tregs
    Shipra Gupta
    Harvard Medical School, Department of Medicine, The Transplant Institute, Beth Israel Deaconess Medical Center, Boston, MA, USA
    J Clin Invest 122:2395-404. 2012
  8. ncbi BTLA is a lymphocyte inhibitory receptor with similarities to CTLA-4 and PD-1
    Norihiko Watanabe
    Department of Pathology and Immunology, Howard Hughes Medical Institute, Washington University School of Medicine, Box 8118, 660 South Euclid Avenue, St Louis, Missouri 63110, USA
    Nat Immunol 4:670-9. 2003
  9. pmc Clonal deletion and the fate of autoreactive thymocytes that survive negative selection
    Leonid A Pobezinsky
    Experimental Immunology Branch, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA
    Nat Immunol 13:569-78. 2012
  10. 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

Research Grants

  1. Activation of innate antiviral defenses by LTbetaR
    CHRISTOPHER BENEDICT; Fiscal Year: 2005

Scientific Experts

Detail Information

Publications122 found, 100 shown here

  1. ncbi PD-1 expression on HIV-specific T cells is associated with T-cell exhaustion and disease progression
    Cheryl L Day
    HIV Pathogenesis Programme, Doris Duke Medical Research Institute, University of KwaZulu Natal, Durban 4013, South Africa
    Nature 443:350-4. 2006
    ..Moreover, this pathway of reversible T-cell impairment provides a potential target for enhancing the function of exhausted T cells in chronic HIV infection...
  2. ncbi Development of lupus-like autoimmune diseases by disruption of the PD-1 gene encoding an ITIM motif-carrying immunoreceptor
    H Nishimura
    Department of Medical Chemistry, Faculty of Medicine, Kyoto University, Japan
    Immunity 11:141-51. 1999
    ..Collectively, it is suggested that PD-1 is involved in the maintenance of peripheral self-tolerance by serving as a negative regulator of immune responses...
  3. ncbi Expression of programmed death 1 ligands by murine T cells and APC
    Tomohide Yamazaki
    Department of Immunology, Juntendo University School of Medicine, 2 1 1 Hongo, Bunkyo ku, Tokyo 113 8421, Japan
    J Immunol 169:5538-45. 2002
    ..The inducible expression of PD-1 ligands on both T cells and APCs may suggest new paradigms of PD-1-mediated immune regulation...
  4. pmc PD-1 and LAG-3 inhibitory co-receptors act synergistically to prevent autoimmunity in mice
    Taku Okazaki
    Division of Immune Regulation, Institute for Genome Research, University of Tokushima, Kuramoto, Tokushima, Japan
    J Exp Med 208:395-407. 2011
    ..In addition, LAG-3 deficiency alone accelerated type 1 diabetes mellitus in nonobese diabetic mice. These results demonstrate that LAG-3 acts synergistically with PD-1 and/or other immunoregulatory genes to prevent autoimmunity in mice...
  5. ncbi PD-1 and PD-1 ligands: from discovery to clinical application
    Taku Okazaki
    21st Century Center of Excellence Formation, Graduate School of Medicine, Kyoto University, Yoshida Konoe, Sakyo ku, Kyoto 606 8501, Japan
    Int Immunol 19:813-24. 2007
    ..In this review, we would like to summarize the history of PD-1 research since its discovery and recent findings that suggest promising future for the clinical application of PD-1 agonists and antagonists to various human diseases...
  6. pmc Coexpression of Tim-3 and PD-1 identifies a CD8+ T-cell exhaustion phenotype in mice with disseminated acute myelogenous leukemia
    Qing Zhou
    Masonic Cancer Center and Department of Pediatrics, Division of Hematology Oncology and Blood and Marrow Transplantation, Kagawa University, Kagawa, Japan
    Blood 117:4501-10. 2011
    ..Therefore, combined PD-1/PDL1 and Tim-3/galectin-9 blockade may be beneficial in preventing CD8(+) T-cell exhaustion in patients with hematologic malignancies such as advanced AML...
  7. pmc Allograft rejection is restrained by short-lived TIM-3+PD-1+Foxp3+ Tregs
    Shipra Gupta
    Harvard Medical School, Department of Medicine, The Transplant Institute, Beth Israel Deaconess Medical Center, Boston, MA, USA
    J Clin Invest 122:2395-404. 2012
    ..However, these TIM-3+ Tregs did not flourish when passively transferred to newly transplanted hosts. These data suggest that a heretofore unrecognized graft-infiltrating, short-lived subset of Tregs can restrain rejection...
  8. ncbi BTLA is a lymphocyte inhibitory receptor with similarities to CTLA-4 and PD-1
    Norihiko Watanabe
    Department of Pathology and Immunology, Howard Hughes Medical Institute, Washington University School of Medicine, Box 8118, 660 South Euclid Avenue, St Louis, Missouri 63110, USA
    Nat Immunol 4:670-9. 2003
    ..B7x, a peripheral homolog of B7, is a ligand of BTLA. Thus, BTLA is a third inhibitory receptor on T lymphocytes with similarities to cytotoxic T lymphocyte-associated antigen 4 (CTLA-4) and programmed death 1 (PD-1)...
  9. pmc Clonal deletion and the fate of autoreactive thymocytes that survive negative selection
    Leonid A Pobezinsky
    Experimental Immunology Branch, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA
    Nat Immunol 13:569-78. 2012
    ..Our study identifies costimulation by CD28 as the intrathymic signal required for clonal deletion and identifies CD8αα(+) IELs as the developmental fate of autoreactive thymocytes that survive negative selection...
  10. 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
    ....
  11. pmc Crystal structure of the complex between programmed death-1 (PD-1) and its ligand PD-L2
    Eszter Lazar-Molnar
    Department of Microbiology and Immunology, Albert Einstein College of Medicine, 1300 Morris Park Avenue, Bronx, NY 10461, USA
    Proc Natl Acad Sci U S A 105:10483-8. 2008
    ..These studies define spatial and organizational constraints that control the localization and signaling of PD-1/PD-L complexes within the immunological synapse and provide a basis for manipulating the PD-1 pathways for immunotherapy...
  12. pmc Cooperative B7-1/2 (CD80/CD86) and B7-DC costimulation of CD4+ T cells independent of the PD-1 receptor
    Tahiro Shin
    Sidneu Kimmel Comprehensive Cancer Centre, Johns Hopkins School of Medicine, Baltimore, MD 21231, USA
    J Exp Med 198:31-8. 2003
    ..Finally, costimulation with B7-DC alone or in conjunction with B7-1 is PD-1 independent, indicating that B7-DC costimulates T cells via a second receptor...
  13. pmc PD-1 deficiency reveals various tissue-specific autoimmunity by H-2b and dose-dependent requirement of H-2g7 for diabetes in NOD mice
    Taku Yoshida
    Department of Immunology and Genomic Medicine, 21st Century Center of Excellence Formation, Graduate School of Medicine, Kyoto University, Yoshida Konoe, Sakyo ku, Kyoto, 606 8501, Japan
    Proc Natl Acad Sci U S A 105:3533-8. 2008
    ..In addition, 60% of the NOD-H2(b/g7)Pdcd1(-/-) mice developed diabetes, suggesting that H-2(b) does not dominantly suppress diabetes and that H-2(g7) induces diabetes in a dose-dependent fashion...
  14. doi Identification of QTLs that modify peripheral neuropathy in NOD.H2b-Pdcd1-/- mice
    Fang Jiang
    Department of Immunology and Genomic Medicine, Kyoto University, Yoshida Konoe, Sakyo ku, Kyoto 606 8501, Japan
    Int Immunol 21:499-509. 2009
    ..These results indicate that NOD genetic background harbors various QTLs that modify autoimmune phenotypes either by organ-specific or by organ-non-specific manner...
  15. pmc PD-1 on dendritic cells impedes innate immunity against bacterial infection
    Sheng Yao
    Department of Oncology and Institute for Cell Engineering, Johns Hopkins University School of Medicine, Baltimore, MD, USA
    Blood 113:5811-8. 2009
    ..Our results reveal a novel role of PD-1 in the negative regulation of DC function during innate immune response...
  16. ncbi Defective induction of CTLA-4 in the NOD mouse is controlled by the NOD allele of Idd3/IL-2 and a novel locus (Ctex) telomeric on chromosome 1
    Marie Lundholm
    Department of Medical Biosciences, Division of Medical and Clinical Genetics, Umea University, Sweden
    Diabetes 55:538-44. 2006
    ..Instead, as previously shown, higher ICOS levels in NOD mice appear to be controlled by gene(s) in the Idd5.1 region, possibly a polymorphism in the Icos gene itself...
  17. ncbi Cutting Edge: Programmed death (PD) ligand-1/PD-1 interaction is required for CD8+ T cell tolerance to tissue antigens
    Natalia Martin-Orozco
    University of Texas M D Anderson Cancer Center, 7455 Fannin, Houston, TX 77030, USA
    J Immunol 177:8291-5. 2006
    ..Thus, during the presentation of tissue Ags to CD8+ T cells, PD-1/PD-L1 interaction crucially controls the effector differentiation of autoreactive T cells to maintain self-tolerance...
  18. pmc Blockade of PD-1/B7-H1 interaction restores effector CD8+ T cell responses in a hepatitis C virus core murine model
    John R Lukens
    Beirne Carter Center for Immunology Research, Department of Microbiology, University of Virginia, Charlottesville, VA 22908, USA
    J Immunol 180:4875-84. 2008
    ..This also suggests that manipulation of the PD-1/B7-H1 pathway may be a potential immunotherapy to enhance effector T cell responses during persistent HCV infection...
  19. pmc Induced expression of PD-1, a novel member of the immunoglobulin gene superfamily, upon programmed cell death
    Y Ishida
    Department of Medical Chemistry, Kyoto University Faculty of Medicine, Japan
    EMBO J 11:3887-95. 1992
    ..These results suggest that activation of the PD-1 gene may be involved in the classical type of programmed cell death...
  20. ncbi Activation-induced expression of human programmed death-1 gene in T-lymphocytes
    R Vibhakar
    Department of Pathology, New York Medical College, Elmsford 10523, USA
    Exp Cell Res 232:25-8. 1997
    ..These data suggest a role for hPD-1 during activation and differentiation of T-lymphocytes...
  21. ncbi Immunological studies on PD-1 deficient mice: implication of PD-1 as a negative regulator for B cell responses
    H Nishimura
    Department of Medical Chemistry, Faculty of Medicine, Kyoto University, Japan
    Int Immunol 10:1563-72. 1998
    ..Thus, PD-1 was suggested to be involved in the negative regulation for particular aspects of B cell proliferation and differentiation including class switching...
  22. pmc Facilitation of beta selection and modification of positive selection in the thymus of PD-1-deficient mice
    H Nishimura
    Department of Medical Chemistry, Graduate School of Medicine, Kyoto University, Kyoto 606 8501, Japan
    J Exp Med 191:891-8. 2000
    ..These results collectively indicate that PD-1 negatively regulates the beta selection and modulates the positive selection, and suggest that PD-1 deficiency may lead to the significant alteration of mature T cell repertoire...
  23. pmc Engagement of the PD-1 immunoinhibitory receptor by a novel B7 family member leads to negative regulation of lymphocyte activation
    G J Freeman
    Department of Adult Oncology, Dana Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts 02115, USA
    J Exp Med 192:1027-34. 2000
    ..PD-L1 expression on nonlymphoid tissues and its potential interaction with PD-1 may subsequently determine the extent of immune responses at sites of inflammation...
  24. ncbi Autoimmune dilated cardiomyopathy in PD-1 receptor-deficient mice
    H Nishimura
    Department of Medical Chemistry, Graduate School of Medicine, Kyoto University, Yoshida konoe cho, Sakyo, Kyoto, 606 8501, Japan
    Science 291:319-22. 2001
    ..These results indicate that PD-1 may be an important factor contributing to the prevention of autoimmune diseases...
  25. ncbi PD-1:PD-L inhibitory pathway affects both CD4(+) and CD8(+) T cells and is overcome by IL-2
    LauraL Carter
    Wyeth Genetics Institute, Cambridge, MA 02140, USA
    Eur J Immunol 32:634-43. 2002
    ..However, CD8(+) T cells may be more sensitive to modulation by the PD-1:PD-L pathway because of their intrinsic inability to produce significant levels of IL-2...
  26. ncbi Differential expression of PD-L1 and PD-L2, ligands for an inhibitory receptor PD-1, in the cells of lymphohematopoietic tissues
    Masayoshi Ishida
    Laboratory of Immunology and Cell Biology, Graduate School of Biostudies, Kyoto University, Kyoto 606 8501, Japan
    Immunol Lett 84:57-62. 2002
    ..Thus, present results demonstrate the distinct expression patterns of PD-L1 and PD-L2 with the cells of lymphohematopoietic tissues exclusively expressing the former...
  27. ncbi Programmed death-1 targeting can promote allograft survival
    Engin Ozkaynak
    Millennium Pharmaceuticals, Cambridge, MA 02139, USA
    J Immunol 169:6546-53. 2002
    ....
  28. pmc PD-1 inhibits antiviral immunity at the effector phase in the liver
    Yoshiko Iwai
    Department of Medical Chemistry, Graduate School of Medicine, Kyoto University, Yoshida, Sakyo ku, Kyoto 606 8501, Japan
    J Exp Med 198:39-50. 2003
    ..These results indicate that PD-1 plays an important role in T cell tolerance at the effector phase and the blockade of the PD-1 pathway can augment antiviral immunity...
  29. pmc The programmed death-1 (PD-1) pathway regulates autoimmune diabetes in nonobese diabetic (NOD) mice
    Mohammed Javeed I Ansari
    Laboratory of Immunogenetics and Transplantation, Brigham and Women s Hospital, Boston, MA 02115, USA
    J Exp Med 198:63-9. 2003
    ....
  30. ncbi Blockade of programmed death-1 engagement accelerates graft-versus-host disease lethality by an IFN-gamma-dependent mechanism
    Bruce R Blazar
    University of Minnesota Cancer Center and Department of Pediatrics, Minneapolis, MN 55455, USA
    J Immunol 171:1272-7. 2003
    ..These data indicate that PD-1 ligation down-regulates GVHD through modulation of IFN-gamma production and suggest a novel therapeutic target for inhibiting GVHD lethality...
  31. ncbi Preferential contribution of B7-H1 to programmed death-1-mediated regulation of hapten-specific allergic inflammatory responses
    Fumihiko Tsushima
    Department of Molecular Immunology, Graduate School, Tokyo Medical and Dental University, Tokyo, Japan
    Eur J Immunol 33:2773-82. 2003
    ..Our results demonstrate the regulatory role of PD-1 and the differential roles of B7-H1 and B7-DC in hapten-induced immune responses. The PD-1-B7-H1 pathway may play a unique role in regulating inflammatory responses...
  32. ncbi Structural and functional analysis of the costimulatory receptor programmed death-1
    Xuewu Zhang
    Department of Cell Biology, Albert Einstein College of Medicine, Bronx, NY 10461 USA
    Immunity 20:337-47. 2004
    ..Furthermore, our structure-based mutagenesis studies identify the ligand binding surface of PD-1, which displays significant differences compared to those present in the other members of the family...
  33. ncbi Suppression of expression and function of negative immune regulator PD-1 by certain pattern recognition and cytokine receptor signals associated with immune system danger
    Xuemei Zhong
    Departments of Medicine, Boston University School of Medicine, Boston University Medical Center, MA 02118, USA
    Int Immunol 16:1181-8. 2004
    ..Our data suggest a novel mechanism for enhancement of normal immune responses and disruption of normal tolerance mechanisms...
  34. ncbi Resting dendritic cells induce peripheral CD8+ T cell tolerance through PD-1 and CTLA-4
    Hans Christian Probst
    Institute of Experimental Immunology, University Hospital Zurich, Switzerland
    Nat Immunol 6:280-6. 2005
    ..Thus PD-1 and CTLA-4 are crucial molecules for peripheral CD8(+) T cell tolerance induced by resting dendritic cells...
  35. pmc Establishment of NOD-Pdcd1-/- mice as an efficient animal model of type I diabetes
    Jian Wang
    Department of Medical Chemistry and Molecular Biology, Graduate School of Medicine, Kyoto University, Yoshida Konoe, Sakyo ku, Kyoto 606 8501, Japan
    Proc Natl Acad Sci U S A 102:11823-8. 2005
    ....
  36. pmc Hydronephrosis associated with antiurothelial and antinuclear autoantibodies in BALB/c-Fcgr2b-/-Pdcd1-/- mice
    Taku Okazaki
    Department of Medical Chemistry and Molecular Biology, Graduate School of Medicine, Kyoto University, Sakyo ku, Kyoto 606 8501, Japan
    J Exp Med 202:1643-8. 2005
    ..These observations suggest cross talk between two immunoinhibitory receptors, FcgammaRIIB and PD-1, on the regulation of autoimmune diseases...
  37. ncbi PD-1/PD-L1, but not PD-1/PD-L2, interactions regulate the severity of experimental autoimmune encephalomyelitis
    Laura L Carter
    Inflammation, Wyeth Research, 200 CambridgePark Dr, Cambridge, MA 02140, United States
    J Neuroimmunol 182:124-34. 2007
    ..These results demonstrate that interactions between PD-1/PD-L1, but not PD-1/PDL-2, are crucial in attenuating T cell responses in EAE...
  38. pmc Interaction between B7-H1 and PD-1 determines initiation and reversal of T-cell anergy
    Fumihiko Tsushima
    Department of Dermatology, Johns Hopkins University School of Medicine, Baltimore, MD 21231, USA
    Blood 110:180-5. 2007
    ..Our results thus reveal previously unappreciated roles of B7-H1 and PD-1 interaction in the control of initiation and reversion of T-cell anergy...
  39. pmc Role of PD-1 and its ligand, B7-H1, in early fate decisions of CD8 T cells
    Monica V Goldberg
    Department of Oncology, Johns Hopkins Sidney Kimmel Comprehensive Cancer Center, Baltimore, MD 21231, USA
    Blood 110:186-92. 2007
    ..These findings demonstrate that, in addition to modulating effector functions in the periphery, B7-H1:PD-1 interactions regulate early T-cell-fate decisions...
  40. ncbi 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...
  41. pmc Proatherogenic immune responses are regulated by the PD-1/PD-L pathway in mice
    Israel Gotsman
    Vascular Research Division, Department of Pathology, Brigham and Women s Hospital, Boston, Massachusetts 02115, USA
    J Clin Invest 117:2974-82. 2007
    ..Our findings indicate that the PD-1/PD-L pathway has an important role in downregulating proatherogenic T cell response and atherosclerosis by limiting APC-dependent T cell activation...
  42. ncbi PD-1 regulates self-reactive CD8+ T cell responses to antigen in lymph nodes and tissues
    Mary E Keir
    Department of Pathology, Harvard Medical School and Brigham and Women s Hospital, Boston, MA 02115, USA
    J Immunol 179:5064-70. 2007
    ....
  43. pmc The PD-1/PD-L costimulatory pathway critically affects host resistance to the pathogenic fungus Histoplasma capsulatum
    Eszter Lazar-Molnar
    Departments of Microbiology and Immunology, Albert Einstein College of Medicine, Yeshiva University, 1300 Morris Park Avenue, Bronx, NY 10461, USA
    Proc Natl Acad Sci U S A 105:2658-63. 2008
    ..The results show that the PD-1/PD-L pathway has a key role in the regulation of antifungal immunity, and suggest that manipulation of this pathway represents a strategy of immunotherapy for histoplasmosis...
  44. pmc Programmed death 1 ligand signaling regulates the generation of adaptive Foxp3+CD4+ regulatory T cells
    Li Wang
    Department of Microbiology and Immunology, Dartmouth Medical School and the Norris Cotton Cancer Center, 1 Medical Center Drive, Lebanon, NH 03756, USA
    Proc Natl Acad Sci U S A 105:9331-6. 2008
    ..Collectively, this study highlights the cellular and molecular parameters that might be exploited to control the de novo generation of aTregs and peripheral tolerance...
  45. doi Fatal autoimmune hepatitis induced by concurrent loss of naturally arising regulatory T cells and PD-1-mediated signaling
    Masahiro Kido
    Department of Gastroenterology and Hepatology, Graduate School of Medicine, Kyoto University, Kyoto, Japan
    Gastroenterology 135:1333-43. 2008
    ..This study aims to examine the regulatory roles of naturally arising CD4(+)CD25(+) regulatory T (Treg) cells and programmed cell death 1 (PD-1)-mediated signaling in the development of AIH...
  46. doi Interferon-sensitive response element (ISRE) is mainly responsible for IFN-alpha-induced upregulation of programmed death-1 (PD-1) in macrophages
    Hae Yun Cho
    Department of Microbiology, Center for Viral Disease Research, Inje University College of Medicine, Busan 614 735, Republic of Korea
    Biochim Biophys Acta 1779:811-9. 2008
    ..Our findings support the essential roles of ISRE, STAT1, and STAT2 in the regulation of constitutive and IFN-alpha-mediated PD-1 expression in macrophages...
  47. pmc Intestinal tolerance is converted to autoimmune enteritis upon PD-1 ligand blockade
    Erika D Reynoso
    Division of Medical Sciences, Harvard Medical School, Boston, MA 02115, USA
    J Immunol 182:2102-12. 2009
    ..Collectively, these results indicate that loss of the PD-1:PD-L1 inhibitory pathway breaks CD8(+) T cell tolerance to intestinal self-Ag, thus leading to severe enteric autoimmunity...
  48. pmc Impact of epitope escape on PD-1 expression and CD8 T-cell exhaustion during chronic infection
    Joseph N Blattman
    Department of Microbiology and Immunology, Emory Vaccine Center, Emory University School of Medicine, Atlanta, Georgia 30322, USA
    J Virol 83:4386-94. 2009
    ....
  49. pmc Recall responses by helpless memory CD8+ T cells are restricted by the up-regulation of PD-1
    Shinichiro Fuse
    Department of Microbiology and Immunology, Dartmouth Medical School, Lebanon, NH 03756, USA
    J Immunol 182:4244-54. 2009
    ....
  50. pmc PD-1 expression by macrophages plays a pathologic role in altering microbial clearance and the innate inflammatory response to sepsis
    Xin Huang
    Division of Surgical Research, Department of Surgery, Brown University School of Medicine Rhode Island Hospital, 593 Eddy Street, Providence, RI 02903, USA
    Proc Natl Acad Sci U S A 106:6303-8. 2009
    ....
  51. pmc Functionally distinct LAG-3 and PD-1 subsets on activated and chronically stimulated CD8 T cells
    Joseph F Grosso
    Department of Oncology, The Johns Hopkins University School of Medicine, Baltimore, MD 21231, USA
    J Immunol 182:6659-69. 2009
    ....
  52. doi Programmed death-1 receptor negatively regulates LPS-mediated IL-12 production and differentiation of murine macrophage RAW264.7 cells
    Hae Yun Cho
    Department of Microbiology, Advanced Research Center for Multiple Myeloma, Inje University College of Medicine, Busan 614 735, Republic of Korea
    Immunol Lett 127:39-47. 2009
    ..7 cells upon PD-1 engagement. Taken together, our results reveal a novel function of macrophage PD-1 in the negative regulation of IL-12 synthesis and differentiation into dendritic cell-like cells...
  53. 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...
  54. pmc PD-1+ memory phenotype CD4+ T cells expressing C/EBPalpha underlie T cell immunodepression in senescence and leukemia
    Kenichiro Shimatani
    Department of Immunology and Cell Biology, Graduate School of Biostudies, Kyoto University, Sakyo ku, Kyoto 606 8501, Japan
    Proc Natl Acad Sci U S A 106:15807-12. 2009
    ..The results suggest that global T cell immunodepression in senescence and leukemia is attributable to the increase in PD-1(+) MP CD4(+) T cells expressing C/EBPalpha...
  55. pmc Tissue-specific differences in PD-1 and PD-L1 expression during chronic viral infection: implications for CD8 T-cell exhaustion
    Shawn D Blackburn
    Department of Medical Oncology, Dana Farber Cancer Center, Department of Medicine, Harvard Medical School, Boston, Massachusetts 02115, USA
    J Virol 84:2078-89. 2010
    ..These observations have implications for human chronic infections and for therapeutic interventions based on blockade of the PD-1 pathway...
  56. doi Dual control of antitumor CD8 T cells through the programmed death-1/programmed death-ligand 1 pathway and immunosuppressive CD4 T cells: regulation and counterregulation
    Andrew J Currie
    National Centre for Asbestos Related Diseases, School of Medicine and Pharmacology, University of Western Australia, Perth, Australia
    J Immunol 183:7898-908. 2009
    ..Thus, PD-L1 blockade activates antitumor CD8 T cell most potently in the absence of CD4 T cells. These findings have implications for the development of PD-L1-based therapies...
  57. pmc PD-1 and CTLA-4 combination blockade expands infiltrating T cells and reduces regulatory T and myeloid cells within B16 melanoma tumors
    Michael A Curran
    Department of Immunology, Howard Hughes Medical Institute, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA
    Proc Natl Acad Sci U S A 107:4275-80. 2010
    ....
  58. doi PD-1 deficiency results in the development of fatal myocarditis in MRL mice
    Jian Wang
    Department of Immunology and Genomic Medicine, Kyoto University, Yoshida Konoe, Sakyo ku, Japan
    Int Immunol 22:443-52. 2010
    ..These findings unravel the hidden heart-specific autoimmune predisposition of MRL mice and provide MRL-Pdcd1(-)(/-) mice as a useful animal model of lymphocytic myocarditis...
  59. pmc PD-1 regulates germinal center B cell survival and the formation and affinity of long-lived plasma cells
    Kim L Good-Jacobson
    Department of Laboratory Medicine, Yale University, New Haven, Connecticut, USA
    Nat Immunol 11:535-42. 2010
    ..PD-1 expression on T cells and PD-L2 expression on B cells controlled T(FH) cell and PC numbers. Thus, PD-1 regulates selection and survival in the GC, affecting the quantity and quality of long-lived PCs...
  60. pmc Deficiency in B7-H1 (PD-L1)/PD-1 coinhibition triggers pancreatic beta-cell destruction by insulin-specific, murine CD8 T-cells
    Tarvo Rajasalu
    Department of Internal Medicine I, University Hospital of Ulm, Ulm, Germany
    Diabetes 59:1966-73. 2010
    ..We tested whether altering the B7-H1 (PD-L1) coinhibition on pancreatic beta-cells can reveal a diabetogenic potential of preproinsulin-specific CD8 T-cells...
  61. pmc Program death-1 signaling and regulatory T cells collaborate to resist the function of adoptively transferred cytotoxic T lymphocytes in advanced acute myeloid leukemia
    Qing Zhou
    Masonic Cancer Center and Department of Pediatrics, Division of Blood and Marrow Transplantation, University of Minnesota, Minneapolis, MN 55455, USA
    Blood 116:2484-93. 2010
    ..PD-1/PD-L1 blockade coupled with Treg depletion represents an important new approach that can be readily translated into the clinic to improve the therapeutic efficacy of adoptive AML-reactive CTLs in advanced AML disease...
  62. pmc Programmed death-1 (PD-1)-deficient mice are extraordinarily sensitive to tuberculosis
    Eszter Lazar-Molnar
    Department of Microbiology and Immunology, Howard Hughes Medical Institute, Albert Einstein College of Medicine, Bronx, NY 10461, USA
    Proc Natl Acad Sci U S A 107:13402-7. 2010
    ..Overall, our studies show that the PD-1 pathway is required to control excessive inflammatory responses after M. tuberculosis infection in the lungs...
  63. pmc Partial restoration of T-cell function in aged mice by in vitro blockade of the PD-1/ PD-L1 pathway
    Celine S Lages
    Cincinnati Children s Hospital Research Foundation, Department of Pediatrics, University of Cincinnati College of Medicine, OH 45229, USA
    Aging Cell 9:785-98. 2010
    ....
  64. pmc Cooperation of Tim-3 and PD-1 in CD8 T-cell exhaustion during chronic viral infection
    Hyun Tak Jin
    Department of Microbiology and Immunology, Emory University School of Medicine, Emory Vaccine Center, Atlanta, GA 30322, USA
    Proc Natl Acad Sci U S A 107:14733-8. 2010
    ....
  65. doi PD-1-PD-L1 pathway impairs T(h)1 immune response in the late stage of infection with Mycobacterium bovis bacillus Calmette-Guérin
    Shunsuke Sakai
    Department of Microbiology, Kyoto University Graduate School of Medicine, Yoshida konoe cho, Sakyo ku, Kyoto 606 8501, Japan
    Int Immunol 22:915-25. 2010
    ..These results indicate that the PD-1-PD-L1 pathway impairs T(h)1 immunity in the late stage of BCG infection, thereby facilitating the bacterial persistence in the host...
  66. pmc CD4 T cells promote rather than control tuberculosis in the absence of PD-1-mediated inhibition
    Daniel L Barber
    Immunobiology Section, Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA
    J Immunol 186:1598-607. 2011
    ..Thus, in the absence of the PD-1 pathway, M. tuberculosis benefits from CD4 T cell responses, and host resistance requires inhibition by PD-1 to prevent T cell-driven exacerbation of the infection...
  67. pmc Regulation of Trypanosoma cruzi-induced myocarditis by programmed death cell receptor 1
    Fredy R S Gutierrez
    Department of Biochemistry and Immunology, School of Medicine of Ribeirao Preto, USP Av Bandeirantes, 3900 Ribeirao Preto, Sao Paulo 14049 900, Brazil
    Infect Immun 79:1873-81. 2011
    ..These results suggest the participation of a PD-1 signaling pathway in the control of acute myocarditis induced by T. cruzi and provide additional insight into the regulatory mechanisms in the pathogenesis of Chagas' disease...
  68. pmc Impairment of the programmed cell death-1 pathway increases atherosclerotic lesion development and inflammation
    De xiu Bu
    Department of Pathology, Brigham and Women s Hospital, and Department of Medicine, Harvard Medical School, NRB Rm 752N, 77 Ave Louis Pasteur, Boston, MA 02115, USA
    Arterioscler Thromb Vasc Biol 31:1100-7. 2011
    ..We studied the contribution of the PD-1 pathway to regulation of T cells that promote atherosclerotic lesion formation and inflammation...
  69. doi The negative costimulatory molecule PD-1 modulates the balance between immunity and tolerance via miR-21
    Dimitrios Iliopoulos
    Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA 02115, USA
    Eur J Immunol 41:1754-63. 2011
    ....
  70. pmc Control of Toxoplasma reactivation by rescue of dysfunctional CD8+ T-cell response via PD-1-PDL-1 blockade
    Rajarshi Bhadra
    Department of Microbiology, George Washington University, Washington, DC 20037, USA
    Proc Natl Acad Sci U S A 108:9196-201. 2011
    ..To the best of our knowledge, this report is unique in showing that exposure to a persistent pathogen despite initial control of parasitemia can lead to CD8(+) T-cell dysfunction and parasite reactivation...
  71. pmc The novel costimulatory programmed death ligand 1/B7.1 pathway is functional in inhibiting alloimmune responses in vivo
    Jun Yang
    Transplantation Research Center, Renal Division, Brigham and Women s Hospital, Harvard Medical School, Boston, MA 02115, USA
    J Immunol 187:1113-9. 2011
    ..1 interaction with T cell PDL1 did not. These data indicate that PDL1 interaction with B7.1 plays an important role in the inhibition of alloimmune responses in vivo and suggests a dominant direction for PDL1 and B7.1 interaction...
  72. pmc Programmed death (PD)-1-deficient mice are extremely sensitive to murine hepatitis virus strain-3 (MHV-3) infection
    Yongwen Chen
    Institute of Immunology, PLA, Third Military Medical University, Chongqing, P R China
    PLoS Pathog 7:e1001347. 2011
    ..Taken together, our results suggest that PD-1 signaling plays an essential role in decreasing the immunopathological damage induced by MHV-3 and that manipulation of this signal might be a useful strategy for FH immunotherapy...
  73. pmc Programmed cell death 1 suppresses B-1b cell expansion and long-lived IgG production in response to T cell-independent type 2 antigens
    Karen M Haas
    Department of Microbiology and Immunology, Wake Forest University School of Medicine, Winston Salem, NC 27157, USA
    J Immunol 187:5183-95. 2011
    ....
  74. pmc Immune inhibitory molecules LAG-3 and PD-1 synergistically regulate T-cell function to promote tumoral immune escape
    Seng Ryong Woo
    Department of Immunology, St Jude Children s Research Hospital, Memphis, Tennessee, USA
    Cancer Res 72:917-27. 2012
    ..In addition, they argue strongly that dual blockade of these molecules represents a promising combinatorial strategy for cancer...
  75. doi The inhibitory receptor PD-1 regulates IgA selection and bacterial composition in the gut
    Shimpei Kawamoto
    Laboratory for Mucosal Immunity, Research Center for Allergy and Immunology, RIKEN Yokohama, Tsurumi, Yokohama, Japan
    Science 336:485-9. 2012
    ..Thus, PD-1 plays a critical role in regulation of antibody diversification required for the maintenance of intact mucosal barrier...
  76. pmc PD-1 blockade enhances T-cell migration to tumors by elevating IFN-γ inducible chemokines
    Weiyi Peng
    Department of Melanoma Medical Oncology, The Center for Cancer Immunology Research, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA
    Cancer Res 72:5209-18. 2012
    ..Taken together, our results imply that blocking the PD-1 pathway can increase IFN-γ at the tumor site, thereby increasing chemokine-dependent trafficking of immune cells into malignant disease sites...
  77. pmc Programmed death 1 protects from fatal circulatory failure during systemic virus infection of mice
    Helge Frebel
    Institute of Microbiology, ETH Zurich, 8093 Zurich, Switzerland
    J Exp Med 209:2485-99. 2012
    ....
  78. doi Programmed death-1 shapes memory phenotype CD8 T cell subsets in a cell-intrinsic manner
    Joanna J Charlton
    Institute of Molecular Biology and Biotechnology, Foundation for Research and Technology Hellas, GR 70013 Heraklion, Crete, Greece
    J Immunol 190:6104-14. 2013
    ..Additionally, adoptively transferred PD-1 KO T(EM) phenotype cells converted to a lesser degree to a T(CM) phenotype. Collectively, these data suggest that PD-1 shapes memory phenotype CD8 T cell subsets...
  79. doi A rheostat for immune responses: the unique properties of PD-1 and their advantages for clinical application
    Taku Okazaki
    Division of Immune Regulation, Institute for Genome Research, University of Tokushima, Tokushima, Japan
    Nat Immunol 14:1212-8. 2013
    ..Such unique properties make PD-1 a powerful target for immunological therapy, with highly effective clinical applications for cancer treatment. ..
  80. ncbi Structure and chromosomal localization of the human PD-1 gene (PDCD1)
    T Shinohara
    Department of Medical Chemistry, Kyoto University Faculty of Medicine, Japan
    Genomics 23:704-6. 1994
    ..The deduced amino acid sequence of human PD-1 was 60% identical to the mouse counterpart, and a putative tyrosine kinase-association motif was well conserved. The human PD-1 gene was mapped to 2q37.3 by chromosomal in situ hybridization...
  81. pmc The CTLA-4 and PD-1/PD-L1 inhibitory pathways independently regulate host resistance to Plasmodium-induced acute immune pathology
    Julius Clemence R Hafalla
    Department of Immunology and Infection, Faculty of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, London, United Kingdom
    PLoS Pathog 8:e1002504. 2012
    ..In summary, our results underscore the differential and complex regulation that governs immune responses to malaria parasites...
  82. pmc PD-1 protects against inflammation and myocyte damage in T cell-mediated myocarditis
    Margarite L Tarrio
    Department of Pathology, Brigham and Women s Hospital, Boston, MA 02115, USA
    J Immunol 188:4876-84. 2012
    ..Together, these studies show that PD-1 plays an important role in limiting T cell responses in the heart...
  83. ncbi Paradoxical role of programmed death-1 ligand 2 in Th2 immune responses in vitro and in a mouse asthma model in vivo
    Ezogelin Oflazoglu
    Department of Inflammation, Amgen Inc, USA
    Eur J Immunol 34:3326-36. 2004
    ..This study provides in vivo evidence of an exacerbated inflammatory response following PD-L2-Fc administration and indicates a potential role for this molecule in Th2-mediated diseases such as asthma...
  84. ncbi Role of the programmed death-1 pathway in regulation of alloimmune responses in vivo
    Sigrid E Sandner
    Transplantation Research Center, Brigham and Women s Hospital, Harvard Medical School, Boston, MA 02115, USA
    J Immunol 174:3408-15. 2005
    ..These data demonstrate a critical role for the PD-1 pathway, particularly PD-1/PD-L1 interactions, in the regulation of alloimmune responses in vivo...
  85. ncbi Bone marrow mesenchymal progenitor cells inhibit lymphocyte proliferation by activation of the programmed death 1 pathway
    Andrea Augello
    Laboratory of Regenerative Medicine, National Institute for Cancer Research, Genova, Italy
    Eur J Immunol 35:1482-90. 2005
    ..Taken together, these results highlight the complexity of the role of BMSC in regulating the immune response, asserting the possibility of their therapeutic application in transplantation and autoimmune diseases...
  86. ncbi Cutting edge: B and T lymphocyte attenuator and programmed death receptor-1 inhibitory receptors are required for termination of acute allergic airway inflammation
    Christine Deppong
    Department of Internal Medicine, Washington University School of Medicine, St Louis, MO 63110, USA
    J Immunol 176:3909-13. 2006
    ..Thus, these receptors are critical determinants of the duration of allergic airway inflammation...
  87. ncbi Treg suppressive activity involves estrogen-dependent expression of programmed death-1 (PD-1)
    Magdalena J Polanczyk
    Neuroimmunology Research, Veterans Affairs Medical Center, R and D 31, 3710 SW US Veterans Hospital Road, Portland, OR 97239, USA
    Int Immunol 19:337-43. 2007
    ..These data clearly demonstrate that E2 can affect multiple regulatory elements that influence Treg suppression, including both PD-1-dependent and PD-1-independent pathways...
  88. ncbi PD-1-PD-L1 pathway is involved in suppressing alloreactivity of heart infiltrating t cells during murine gvhd across minor histocompatibility antigen barriers
    Karin Schilbach
    Children s Hospital, University of Tuebingen, Tuebingen, Germany
    Transplantation 84:214-22. 2007
    ..In the present study, we wanted to investigate whether local regulatory T cells (Treg) or differential expression of immunomodulatory molecules contribute to organ specificity of GVHD...
  89. doi The co-inhibitory molecule PD-1 modulates disease severity in a model for an inherited, demyelinating neuropathy
    Antje Kroner
    Department of Neurology, University of Wuerzburg, Wuerzburg
    Neurobiol Dis 33:96-103. 2009
    ....
  90. pmc PD-1 regulates neural damage in oligodendroglia-induced inflammation
    Antje Kroner
    Department of Neurology, University of Wuerzburg, Wuerzburg, Germany
    PLoS ONE 4:e4405. 2009
    ..Our finding may have implications for understanding the mechanisms leading to the high clinical variability of polygenic or even monogenic disorders of the nervous system...
  91. pmc PD-1/PD-L1 interactions inhibit antitumor immune responses in a murine acute myeloid leukemia model
    Long Zhang
    Department of Medicine, University of Chicago, Chicago, IL 60637, USA
    Blood 114:1545-52. 2009
    ..These data suggest the importance of the PD-1/PD-L1 pathway in immune evasion by a hematologic malignancy, providing a rationale for clinical trials targeting this pathway in leukemia patients...
  92. doi Cutting edge: CD28 engagement releases antigen-activated invariant NKT cells from the inhibitory effects of PD-1
    Jianxiong Wang
    Department of Biochemistry and Molecular Biology, Julia McFarlane Diabetes Research Centre, Faculty of Medicine, University of Calgary, Calgary, Alberta, Canada
    J Immunol 182:6644-7. 2009
    ..The opposing functions of CD28 and PD-1 thus tightly regulate the unique effector function iNKT cells...
  93. doi Altered availability of PD-1/PD ligands is associated with the failure to control autoimmunity in NOD mice
    Deepak Yadav
    Department of Immunology, The Scripps Research Institute, La Jolla, CA 92037, United States
    Cell Immunol 258:161-71. 2009
    ..In summary, these data suggest that diabetes susceptibility in NOD mice is associated with altered PD-1/PD-L availability...
  94. doi Ncf1-associated reduced oxidative burst promotes IL-33R+ T cell-mediated adjuvant-free arthritis in mice
    Kristin Hagenow
    Medical Inflammation Research, Lund University and Karolinska Institute, Stockholm, Sweden
    J Immunol 183:874-81. 2009
    ..These results demonstrate that the insufficient production of ROS promotes the breakdown of immune tolerance and development of autoimmune and adjuvant-free arthritis through an IL-5- and IL33R-dependent T cell activation pathway...
  95. pmc Early CD4(+) T cell help prevents partial CD8(+) T cell exhaustion and promotes maintenance of Herpes Simplex Virus 1 latency
    Gregory M Frank
    Graduate Program in Immunology, University of Pittsburgh School of Medicine, Pittsburgh, PA 15213, USA
    J Immunol 184:277-86. 2010
    ..CD4(+) T cells are not needed to maintain CD8(+) T cell memory through 34 d after infection, nor do they have a direct involvement in the maintenance of HSV-1 latency...
  96. doi Suppression of bystander T helper 1 cells by iris pigment epithelium-inducing regulatory T cells via negative costimulatory signals
    Sunao Sugita
    Department of Ophthalmology and Visual Science, Tokyo Medical and Dental University Graduate School, Tokyo, Japan
    Invest Ophthalmol Vis Sci 51:2529-36. 2010
    ..To determine whether iris pigment epithelium (IPE)-induced T regulatory (Treg) cells can suppress the activation of bystander T cells with cell contact via costimulatory interactions...
  97. ncbi [Protection of PD-1 against LPS-induced endotoxemia and the underlying mechanism]
    Li Fen Yang
    Department of Pediatrics, Xiangya Hospital, Central South University, Changsha, China
    Zhongguo Dang Dai Er Ke Za Zhi 12:812-5. 2010
    ..The member of immunoglobulin family programmed death-1 (PD-1) is a negative immune regulator. This study investigated the protective effect of PD-1 as well as the underlying mechanism in LPS-induced endotoxemia...
  98. doi Programmed death-1 is required for systemic self-tolerance in newly generated T cells during the establishment of immune homeostasis
    G Thangavelu
    Department of Surgery, University of Alberta, Edmonton, Alberta, Canada
    J Autoimmun 36:301-12. 2011
    ....
  99. ncbi The human PD-1 gene: complete cDNA, genomic organization, and developmentally regulated expression in B cell progenitors
    L R Finger
    Department of Medicine, New York Medical College, Elmsford 10523, USA
    Gene 197:177-87. 1997
    ..These data suggest that PD-1 may play a role in B-cell differentiation during the pro-B cell stage...
  100. ncbi Programmed death-1-programmed death-L1 interaction is essential for induction of regulatory cells by intratracheal delivery of alloantigen
    Osamu Aramaki
    Third Department of Surgery, Nihon University, Tokyo, Japan
    Transplantation 77:6-12. 2004
    ..Programmed death (PD)-1 has been implicated in peripheral tolerance. The authors investigated the roles of PD-1 and its ligands, PD-L1 and PD-L2, in the induction of regulatory cells by intratracheal delivery of alloantigen...
  101. ncbi B and T lymphocyte attenuator regulates T cell activation through interaction with herpesvirus entry mediator
    John R Sedy
    Department of Pathology and Center for Immunology, Washington University School of Medicine, St Louis, Missouri 63110, USA
    Nat Immunol 6:90-8. 2005
    ..The conservation of the BTLA-HVEM interaction between mouse and human suggests that this system is an important pathway regulating lymphocyte activation and/or homeostasis in the immune response...

Research Grants1

  1. Activation of innate antiviral defenses by LTbetaR
    CHRISTOPHER BENEDICT; Fiscal Year: 2005
    ..abstract_text> ..