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
Products:     PD 1

Top Publications

  1. Sage P, Francisco L, Carman C, Sharpe A. The receptor PD-1 controls follicular regulatory T cells in the lymph nodes and blood. Nat Immunol. 2013;14:152-61 pubmed publisher
    ..Our findings demonstrate mechanisms by which the PD-1 pathway regulates antibody production and help reconcile inconsistencies surrounding the role of this pathway in humoral immunity...
  2. Ishida Y, Agata Y, Shibahara K, Honjo T. Induced expression of PD-1, a novel member of the immunoglobulin gene superfamily, upon programmed cell death. EMBO J. 1992;11:3887-95 pubmed
    ..These results suggest that activation of the PD-1 gene may be involved in the classical type of programmed cell death. ..
  3. Lazar Molnar E, Gacser A, Freeman G, Almo S, Nathenson S, Nosanchuk J. The PD-1/PD-L costimulatory pathway critically affects host resistance to the pathogenic fungus Histoplasma capsulatum. Proc Natl Acad Sci U S A. 2008;105:2658-63 pubmed publisher
    ..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. ..
  4. Guleria I, Gubbels Bupp M, Dada S, Fife B, Tang Q, Ansari M, et al. Mechanisms of PDL1-mediated regulation of autoimmune diabetes. Clin Immunol. 2007;125:16-25 pubmed
    ..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. ..
  5. Okazaki T, Okazaki I, Wang J, Sugiura D, Nakaki F, Yoshida T, et al. PD-1 and LAG-3 inhibitory co-receptors act synergistically to prevent autoimmunity in mice. J Exp Med. 2011;208:395-407 pubmed publisher
    ..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. ..
  6. Tsushima F, Yao S, Shin T, Flies A, Flies S, Xu H, et al. Interaction between B7-H1 and PD-1 determines initiation and reversal of T-cell anergy. Blood. 2007;110:180-5 pubmed
    ..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. ..
  7. Yamazaki T, Akiba H, Iwai H, Matsuda H, Aoki M, Tanno Y, et al. Expression of programmed death 1 ligands by murine T cells and APC. J Immunol. 2002;169:5538-45 pubmed
    ..The inducible expression of PD-1 ligands on both T cells and APCs may suggest new paradigms of PD-1-mediated immune regulation...
  8. Zhou Q, Munger M, Veenstra R, Weigel B, Hirashima M, Munn D, et al. Coexpression of Tim-3 and PD-1 identifies a CD8+ T-cell exhaustion phenotype in mice with disseminated acute myelogenous leukemia. Blood. 2011;117:4501-10 pubmed publisher
    ..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. ..
  9. Sakai S, Kawamura I, Okazaki T, Tsuchiya K, Uchiyama R, Mitsuyama M. PD-1-PD-L1 pathway impairs T(h)1 immune response in the late stage of infection with Mycobacterium bovis bacillus Calmette-Guérin. Int Immunol. 2010;22:915-25 pubmed publisher
    ..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. ..

More Information

Publications81

  1. Nishimura H, Okazaki T, Tanaka Y, Nakatani K, Hara M, Matsumori A, et al. Autoimmune dilated cardiomyopathy in PD-1 receptor-deficient mice. Science. 2001;291:319-22 pubmed
    ..These results indicate that PD-1 may be an important factor contributing to the prevention of autoimmune diseases. ..
  2. Currie A, Prosser A, McDonnell A, Cleaver A, Robinson B, Freeman G, et al. 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. J Immunol. 2009;183:7898-908 pubmed publisher
    ..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. ..
  3. Lukens J, Cruise M, Lassen M, Hahn Y. Blockade of PD-1/B7-H1 interaction restores effector CD8+ T cell responses in a hepatitis C virus core murine model. J Immunol. 2008;180:4875-84 pubmed
    ..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. ..
  4. Blazar B, Carreno B, Panoskaltsis Mortari A, Carter L, Iwai Y, Yagita H, et al. Blockade of programmed death-1 engagement accelerates graft-versus-host disease lethality by an IFN-gamma-dependent mechanism. J Immunol. 2003;171:1272-7 pubmed
    ..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. ..
  5. Yang J, Riella L, Chock S, Liu T, Zhao X, Yuan X, et al. The novel costimulatory programmed death ligand 1/B7.1 pathway is functional in inhibiting alloimmune responses in vivo. J Immunol. 2011;187:1113-9 pubmed publisher
    ..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. ..
  6. Cho H, Lee S, Seo S, Choi I, Choi I, Lee S. Interferon-sensitive response element (ISRE) is mainly responsible for IFN-alpha-induced upregulation of programmed death-1 (PD-1) in macrophages. Biochim Biophys Acta. 2008;1779:811-9 pubmed publisher
    ..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. ..
  7. Tsushima F, Iwai H, Otsuki N, Abe M, Hirose S, Yamazaki T, et al. Preferential contribution of B7-H1 to programmed death-1-mediated regulation of hapten-specific allergic inflammatory responses. Eur J Immunol. 2003;33:2773-82 pubmed
    ..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. ..
  8. Nishimura H, Minato N, Nakano T, Honjo T. Immunological studies on PD-1 deficient mice: implication of PD-1 as a negative regulator for B cell responses. Int Immunol. 1998;10:1563-72 pubmed
    ..Thus, PD-1 was suggested to be involved in the negative regulation for particular aspects of B cell proliferation and differentiation including class switching. ..
  9. Wang L, Pino Lagos K, de Vries V, Guleria I, Sayegh M, Noelle R. Programmed death 1 ligand signaling regulates the generation of adaptive Foxp3+CD4+ regulatory T cells. Proc Natl Acad Sci U S A. 2008;105:9331-6 pubmed publisher
    ..Collectively, this study highlights the cellular and molecular parameters that might be exploited to control the de novo generation of aTregs and peripheral tolerance. ..
  10. Martin Orozco N, Wang Y, Yagita H, Dong C. Cutting Edge: Programmed death (PD) ligand-1/PD-1 interaction is required for CD8+ T cell tolerance to tissue antigens. J Immunol. 2006;177:8291-5 pubmed
    ..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. ..
  11. Wang J, Okazaki I, Yoshida T, Chikuma S, Kato Y, Nakaki F, et al. PD-1 deficiency results in the development of fatal myocarditis in MRL mice. Int Immunol. 2010;22:443-52 pubmed publisher
    ..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. ..
  12. Zhong X, Bai C, Gao W, Strom T, Rothstein T. Suppression of expression and function of negative immune regulator PD-1 by certain pattern recognition and cytokine receptor signals associated with immune system danger. Int Immunol. 2004;16:1181-8 pubmed
    ..Our data suggest a novel mechanism for enhancement of normal immune responses and disruption of normal tolerance mechanisms. ..
  13. Lazar Molnar E, Chen B, Sweeney K, Wang E, Liu W, Lin J, et al. Programmed death-1 (PD-1)-deficient mice are extraordinarily sensitive to tuberculosis. Proc Natl Acad Sci U S A. 2010;107:13402-7 pubmed publisher
    ..Overall, our studies show that the PD-1 pathway is required to control excessive inflammatory responses after M. tuberculosis infection in the lungs. ..
  14. Rajasalu T, Brosi H, Schuster C, Spyrantis A, Boehm B, Chen L, et al. Deficiency in B7-H1 (PD-L1)/PD-1 coinhibition triggers pancreatic beta-cell destruction by insulin-specific, murine CD8 T-cells. Diabetes. 2010;59:1966-73 pubmed publisher
    ..Hence, regulation of the susceptibility of the beta-cells for a preproinsulin-specific CD8 T-cell attack can allow or suppress EAD. ..
  15. Okazaki T, Otaka Y, Wang J, Hiai H, Takai T, Ravetch J, et al. Hydronephrosis associated with antiurothelial and antinuclear autoantibodies in BALB/c-Fcgr2b-/-Pdcd1-/- mice. J Exp Med. 2005;202:1643-8 pubmed
    ..These observations suggest cross talk between two immunoinhibitory receptors, FcgammaRIIB and PD-1, on the regulation of autoimmune diseases. ..
  16. Iwai Y, Terawaki S, Ikegawa M, Okazaki T, Honjo T. PD-1 inhibits antiviral immunity at the effector phase in the liver. J Exp Med. 2003;198:39-50 pubmed
    ..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. ..
  17. Gotsman I, Grabie N, Dacosta R, Sukhova G, Sharpe A, Lichtman A. Proatherogenic immune responses are regulated by the PD-1/PD-L pathway in mice. J Clin Invest. 2007;117:2974-82 pubmed
    ..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. ..
  18. Peng W, Liu C, Xu C, Lou Y, Chen J, Yang Y, et al. PD-1 blockade enhances T-cell migration to tumors by elevating IFN-? inducible chemokines. Cancer Res. 2012;72:5209-18 pubmed publisher
    ..Taken together, our results imply that blocking the PD-1 pathway can increase IFN-? at the tumor site, thereby increasing chemokine-dependent trafficking of immune cells into malignant disease sites. ..
  19. Okazaki T, Chikuma S, Iwai Y, Fagarasan S, Honjo T. A rheostat for immune responses: the unique properties of PD-1 and their advantages for clinical application. Nat Immunol. 2013;14:1212-8 pubmed publisher
    ..Such unique properties make PD-1 a powerful target for immunological therapy, with highly effective clinical applications for cancer treatment. ..
  20. Nishimura H, Nose M, Hiai H, Minato N, Honjo T. Development of lupus-like autoimmune diseases by disruption of the PD-1 gene encoding an ITIM motif-carrying immunoreceptor. Immunity. 1999;11:141-51 pubmed
    ..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. ..
  21. Frebel H, Nindl V, Schuepbach R, Braunschweiler T, Richter K, Vogel J, et al. Programmed death 1 protects from fatal circulatory failure during systemic virus infection of mice. J Exp Med. 2012;209:2485-99 pubmed publisher
  22. Curran M, Montalvo W, Yagita H, Allison J. PD-1 and CTLA-4 combination blockade expands infiltrating T cells and reduces regulatory T and myeloid cells within B16 melanoma tumors. Proc Natl Acad Sci U S A. 2010;107:4275-80 pubmed publisher
  23. Chen Y, Wu S, Guo G, Fei L, Guo S, Yang C, et al. Programmed death (PD)-1-deficient mice are extremely sensitive to murine hepatitis virus strain-3 (MHV-3) infection. PLoS Pathog. 2011;7:e1001347 pubmed publisher
    ..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...
  24. Kido M, Watanabe N, Okazaki T, Akamatsu T, Tanaka J, Saga K, et al. Fatal autoimmune hepatitis induced by concurrent loss of naturally arising regulatory T cells and PD-1-mediated signaling. Gastroenterology. 2008;135:1333-43 pubmed publisher
    ..Autoreactive CD4(+) T cells are essential for induction of AIH, whereas CD8(+) T cells play an important role in progression to fatal hepatic damage. ..
  25. Grosso J, Goldberg M, Getnet D, Bruno T, Yen H, Pyle K, et al. Functionally distinct LAG-3 and PD-1 subsets on activated and chronically stimulated CD8 T cells. J Immunol. 2009;182:6659-69 pubmed publisher
  26. Fife B, Pauken K, Eagar T, Obu T, Wu J, Tang Q, et al. Interactions between PD-1 and PD-L1 promote tolerance by blocking the TCR-induced stop signal. Nat Immunol. 2009;10:1185-92 pubmed publisher
    ..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...
  27. Fife B, Guleria I, Gubbels Bupp M, Eagar T, Tang Q, Bour Jordan H, et al. Insulin-induced remission in new-onset NOD mice is maintained by the PD-1-PD-L1 pathway. J Exp Med. 2006;203:2737-47 pubmed
  28. Day C, Kaufmann D, Kiepiela P, Brown J, Moodley E, Reddy S, et al. PD-1 expression on HIV-specific T cells is associated with T-cell exhaustion and disease progression. Nature. 2006;443:350-4 pubmed
    ..Moreover, this pathway of reversible T-cell impairment provides a potential target for enhancing the function of exhausted T cells in chronic HIV infection. ..
  29. Bu D, Tarrio M, Maganto Garcia E, Stavrakis G, Tajima G, Lederer J, et al. Impairment of the programmed cell death-1 pathway increases atherosclerotic lesion development and inflammation. Arterioscler Thromb Vasc Biol. 2011;31:1100-7 pubmed publisher
    ..PD-1 has an important role in downregulating proatherogenic T-cell responses, and blockade of this molecule for treatment of viral infections or cancer may increase risk of cardiovascular complications. ..
  30. Bhadra R, Gigley J, Weiss L, Khan I. Control of Toxoplasma reactivation by rescue of dysfunctional CD8+ T-cell response via PD-1-PDL-1 blockade. Proc Natl Acad Sci U S A. 2011;108:9196-201 pubmed publisher
    ..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. ..
  31. Okazaki T, Tanaka Y, Nishio R, Mitsuiye T, Mizoguchi A, Wang J, et al. Autoantibodies against cardiac troponin I are responsible for dilated cardiomyopathy in PD-1-deficient mice. Nat Med. 2003;9:1477-83 pubmed
    ..These findings suggest that antibodies to cTnI induce heart dysfunction and dilatation by chronic stimulation of Ca2+ influx in cardiomyocytes. ..
  32. Shin T, Kennedy G, Gorski K, Tsuchiya H, Koseki H, Azuma M, et al. Cooperative B7-1/2 (CD80/CD86) and B7-DC costimulation of CD4+ T cells independent of the PD-1 receptor. J Exp Med. 2003;198:31-8 pubmed
    ..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. ..
  33. Kawamoto S, Tran T, Maruya M, Suzuki K, Doi Y, Tsutsui Y, et al. The inhibitory receptor PD-1 regulates IgA selection and bacterial composition in the gut. Science. 2012;336:485-9 pubmed publisher
    ..Thus, PD-1 plays a critical role in regulation of antibody diversification required for the maintenance of intact mucosal barrier...
  34. Jin H, Anderson A, Tan W, West E, Ha S, Araki K, et al. Cooperation of Tim-3 and PD-1 in CD8 T-cell exhaustion during chronic viral infection. Proc Natl Acad Sci U S A. 2010;107:14733-8 pubmed publisher
  35. Zhou Q, Munger M, Highfill S, Tolar J, Weigel B, Riddle M, et al. Program death-1 signaling and regulatory T cells collaborate to resist the function of adoptively transferred cytotoxic T lymphocytes in advanced acute myeloid leukemia. Blood. 2010;116:2484-93 pubmed publisher
    ..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...
  36. Blackburn S, Crawford A, Shin H, Polley A, Freeman G, Wherry E. Tissue-specific differences in PD-1 and PD-L1 expression during chronic viral infection: implications for CD8 T-cell exhaustion. J Virol. 2010;84:2078-89 pubmed publisher
    ..These observations have implications for human chronic infections and for therapeutic interventions based on blockade of the PD-1 pathway. ..
  37. Charlton J, Chatzidakis I, Tsoukatou D, Boumpas D, Garinis G, Mamalaki C. Programmed death-1 shapes memory phenotype CD8 T cell subsets in a cell-intrinsic manner. J Immunol. 2013;190:6104-14 pubmed publisher
    ..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. ..
  38. Blattman J, Wherry E, Ha S, van der Most R, Ahmed R. Impact of epitope escape on PD-1 expression and CD8 T-cell exhaustion during chronic infection. J Virol. 2009;83:4386-94 pubmed publisher
  39. Huang X, Venet F, Wang Y, Lepape A, Yuan Z, Chen Y, et al. PD-1 expression by macrophages plays a pathologic role in altering microbial clearance and the innate inflammatory response to sepsis. Proc Natl Acad Sci U S A. 2009;106:6303-8 pubmed publisher
  40. Ishida M, Iwai Y, Tanaka Y, Okazaki T, Freeman G, Minato N, et al. Differential expression of PD-L1 and PD-L2, ligands for an inhibitory receptor PD-1, in the cells of lymphohematopoietic tissues. Immunol Lett. 2002;84:57-62 pubmed
    ..Thus, present results demonstrate the distinct expression patterns of PD-L1 and PD-L2 with the cells of lymphohematopoietic tissues exclusively expressing the former. ..
  41. Jiang F, Yoshida T, Nakaki F, Terawaki S, Chikuma S, Kato Y, et al. Identification of QTLs that modify peripheral neuropathy in NOD.H2b-Pdcd1-/- mice. Int Immunol. 2009;21:499-509 pubmed publisher
    ..These results indicate that NOD genetic background harbors various QTLs that modify autoimmune phenotypes either by organ-specific or by organ-non-specific manner. ..
  42. Wang J, Yoshida T, Nakaki F, Hiai H, Okazaki T, Honjo T. Establishment of NOD-Pdcd1-/- mice as an efficient animal model of type I diabetes. Proc Natl Acad Sci U S A. 2005;102:11823-8 pubmed
  43. Keir M, Freeman G, Sharpe A. PD-1 regulates self-reactive CD8+ T cell responses to antigen in lymph nodes and tissues. J Immunol. 2007;179:5064-70 pubmed
  44. Nishimura H, Honjo T, Minato N. Facilitation of beta selection and modification of positive selection in the thymus of PD-1-deficient mice. J Exp Med. 2000;191:891-8 pubmed
    ..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. ..
  45. Barber D, Mayer Barber K, Feng C, Sharpe A, Sher A. CD4 T cells promote rather than control tuberculosis in the absence of PD-1-mediated inhibition. J Immunol. 2011;186:1598-607 pubmed publisher
    ..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. ..
  46. Pobezinsky L, Angelov G, Tai X, Jeurling S, Van Laethem F, Feigenbaum L, et al. Clonal deletion and the fate of autoreactive thymocytes that survive negative selection. Nat Immunol. 2012;13:569-78 pubmed publisher
    ..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. ..
  47. Carter L, Fouser L, Jussif J, Fitz L, Deng B, Wood C, et al. PD-1:PD-L inhibitory pathway affects both CD4(+) and CD8(+) T cells and is overcome by IL-2. Eur J Immunol. 2002;32:634-43 pubmed
    ..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. ..
  48. Good Jacobson K, Szumilas C, Chen L, Sharpe A, Tomayko M, Shlomchik M. PD-1 regulates germinal center B cell survival and the formation and affinity of long-lived plasma cells. Nat Immunol. 2010;11:535-42 pubmed publisher
    ..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. ..
  49. Shimatani K, Nakashima Y, Hattori M, Hamazaki Y, Minato N. PD-1+ memory phenotype CD4+ T cells expressing C/EBPalpha underlie T cell immunodepression in senescence and leukemia. Proc Natl Acad Sci U S A. 2009;106:15807-12 pubmed publisher
    ..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. ..
  50. Fuse S, Tsai C, Molloy M, Allie S, Zhang W, Yagita H, et al. Recall responses by helpless memory CD8+ T cells are restricted by the up-regulation of PD-1. J Immunol. 2009;182:4244-54 pubmed publisher
  51. Duraiswamy J, Kaluza K, Freeman G, Coukos G. Dual blockade of PD-1 and CTLA-4 combined with tumor vaccine effectively restores T-cell rejection function in tumors. Cancer Res. 2013;73:3591-603 pubmed publisher
  52. Raptopoulou A, Bertsias G, Makrygiannakis D, Verginis P, Kritikos I, Tzardi M, et al. The programmed death 1/programmed death ligand 1 inhibitory pathway is up-regulated in rheumatoid synovium and regulates peripheral T cell responses in human and murine arthritis. Arthritis Rheum. 2010;62:1870-80 pubmed publisher
    ..The negative costimulatory PD-1/PDL-1 pathway regulates peripheral T cell responses in both human and murine RA. PD-1/PDL-1 in rheumatoid synovium may represent an additional target for immunomodulatory therapy in RA. ..
  53. Goldberg M, Maris C, Hipkiss E, Flies A, Zhen L, Tuder R, et al. Role of PD-1 and its ligand, B7-H1, in early fate decisions of CD8 T cells. Blood. 2007;110:186-92 pubmed
    ..These findings demonstrate that, in addition to modulating effector functions in the periphery, B7-H1:PD-1 interactions regulate early T-cell-fate decisions. ..
  54. Carter L, Leach M, Azoitei M, Cui J, Pelker J, Jussif J, et al. PD-1/PD-L1, but not PD-1/PD-L2, interactions regulate the severity of experimental autoimmune encephalomyelitis. J Neuroimmunol. 2007;182:124-34 pubmed
    ..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. ..
  55. Iliopoulos D, Kavousanaki M, Ioannou M, Boumpas D, Verginis P. The negative costimulatory molecule PD-1 modulates the balance between immunity and tolerance via miR-21. Eur J Immunol. 2011;41:1754-63 pubmed publisher
  56. Okazaki T, Honjo T. PD-1 and PD-1 ligands: from discovery to clinical application. Int Immunol. 2007;19:813-24 pubmed
    ..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. ..
  57. Kao C, Oestreich K, Paley M, Crawford A, Angelosanto J, Ali M, et al. Transcription factor T-bet represses expression of the inhibitory receptor PD-1 and sustains virus-specific CD8+ T cell responses during chronic infection. Nat Immunol. 2011;12:663-71 pubmed publisher
    ..Persistent antigenic stimulation caused downregulation of T-bet, which resulted in more severe exhaustion of CD8(+) T cells. Our observations suggest therapeutic opportunities involving higher T-bet expression during chronic infection...
  58. Zhang X, Schwartz J, Guo X, Bhatia S, Cao E, Lorenz M, et al. Structural and functional analysis of the costimulatory receptor programmed death-1. Immunity. 2004;20:337-47 pubmed
    ..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. ..
  59. Haas K. Programmed cell death 1 suppresses B-1b cell expansion and long-lived IgG production in response to T cell-independent type 2 antigens. J Immunol. 2011;187:5183-95 pubmed publisher
  60. Yokosuka T, Takamatsu M, Kobayashi Imanishi W, Hashimoto Tane A, Azuma M, Saito T. Programmed cell death 1 forms negative costimulatory microclusters that directly inhibit T cell receptor signaling by recruiting phosphatase SHP2. J Exp Med. 2012;209:1201-17 pubmed publisher
    ..This inhibitory mechanism also functions in PD-1(hi) T cells generated in vivo and can be overridden by a neutralizing anti-PD-L1 antibody. Therefore, PD-1 microcluster formation is important for regulation of T cell activation. ..
  61. Ozkaynak E, Wang L, Goodearl A, McDonald K, Qin S, O Keefe T, et al. Programmed death-1 targeting can promote allograft survival. J Immunol. 2002;169:6546-53 pubmed
  62. Bhadra R, Gigley J, Khan I. PD-1-mediated attrition of polyfunctional memory CD8+ T cells in chronic toxoplasma infection. J Infect Dis. 2012;206:125-34 pubmed publisher
    ..The conclusions of this study can have profound immunotherapeutic implications in combating recrudescent toxoplasmosis as well other chronic infections. ..
  63. Lazar Molnar E, Yan Q, Cao E, Ramagopal U, Nathenson S, Almo S. Crystal structure of the complex between programmed death-1 (PD-1) and its ligand PD-L2. Proc Natl Acad Sci U S A. 2008;105:10483-8 pubmed publisher
    ..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. ..
  64. Yao S, Wang S, Zhu Y, Luo L, Zhu G, Flies S, et al. PD-1 on dendritic cells impedes innate immunity against bacterial infection. Blood. 2009;113:5811-8 pubmed publisher
    ..Our results reveal a novel role of PD-1 in the negative regulation of DC function during innate immune response. ..
  65. Vibhakar R, Juan G, Traganos F, Darzynkiewicz Z, Finger L. Activation-induced expression of human programmed death-1 gene in T-lymphocytes. Exp Cell Res. 1997;232:25-8 pubmed
    ..These data suggest a role for hPD-1 during activation and differentiation of T-lymphocytes. ..
  66. Woo S, Turnis M, Goldberg M, Bankoti J, Selby M, Nirschl C, et al. Immune inhibitory molecules LAG-3 and PD-1 synergistically regulate T-cell function to promote tumoral immune escape. Cancer Res. 2012;72:917-27 pubmed publisher
    ..In addition, they argue strongly that dual blockade of these molecules represents a promising combinatorial strategy for cancer. ..
  67. Ansari M, Salama A, Chitnis T, Smith R, Yagita H, Akiba H, et al. The programmed death-1 (PD-1) pathway regulates autoimmune diabetes in nonobese diabetic (NOD) mice. J Exp Med. 2003;198:63-9 pubmed
  68. Lages C, Lewkowich I, Sproles A, Wills Karp M, Chougnet C. Partial restoration of T-cell function in aged mice by in vitro blockade of the PD-1/?PD-L1 pathway. Aging Cell. 2010;9:785-98 pubmed publisher
  69. Reynoso E, Elpek K, Francisco L, Bronson R, Bellemare Pelletier A, Sharpe A, et al. Intestinal tolerance is converted to autoimmune enteritis upon PD-1 ligand blockade. J Immunol. 2009;182:2102-12 pubmed publisher
    ..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. ..
  70. Probst H, McCoy K, Okazaki T, Honjo T, Van Den Broek M. Resting dendritic cells induce peripheral CD8+ T cell tolerance through PD-1 and CTLA-4. Nat Immunol. 2005;6:280-6 pubmed
    ..Thus PD-1 and CTLA-4 are crucial molecules for peripheral CD8(+) T cell tolerance induced by resting dendritic cells. ..
  71. Yoshida T, Jiang F, Honjo T, Okazaki T. PD-1 deficiency reveals various tissue-specific autoimmunity by H-2b and dose-dependent requirement of H-2g7 for diabetes in NOD mice. Proc Natl Acad Sci U S A. 2008;105:3533-8 pubmed publisher
    ..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. ..
  72. Shinohara T, Taniwaki M, Ishida Y, Kawaichi M, Honjo T. Structure and chromosomal localization of the human PD-1 gene (PDCD1). Genomics. 1994;23:704-6 pubmed
    ..The human PD-1 gene was mapped to 2q37.3 by chromosomal in situ hybridization. ..