Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Review Article
  • Published:

The function of programmed cell death 1 and its ligands in regulating autoimmunity and infection

Nature Immunology volume 8, pages 239–245 (2007)Cite this article

Abstract

The programmed cell death 1 (PD-1) surface receptor binds to two ligands, PD-L1 and PD-L2. Studies have shown that PD-1–PD-L interactions control the induction and maintenance of peripheral T cell tolerance and indicate a previously unknown function for PD-L1 on nonhematopoietic cells in protecting tissues from autoimmune attack. PD-1 and its ligands have also been exploited by a variety of microorganisms to attenuate antimicrobial immunity and facilitate chronic infection. Here we examine the functions of PD-1 and its ligands in regulating antimicrobial and self-reactive T cell responses and discuss the therapeutic potential of manipulating this pathway.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Figure 1: The PD-1–PD-L pathway controls autoimmunity.
Figure 2: The PD-1–PD-L pathway contributes directly to T cell dysfunction and lack of viral control during chronic viral infection.
Figure 3: Infection with parasites can upregulate PD-L on macrophages that induce T cell anergy.

Similar content being viewed by others

References

  1. Greenwald, R.J., Freeman, G.J. & Sharpe, A.H. The B7 family revisited. Annu. Rev. Immunol. 23, 515–548 (2005).An excellent review on pseudotyped lentiviral vectors. Targeting of particular organs or cell types (for example, neurons, airway epithelia, tumours and others) is emphasized.

    PubMed  Google Scholar 

  2. Okazaki, T. & Honjo, T. The PD-1-PD-L pathway in immunological tolerance. Trends Immunol. 27, 195–201 (2006).The initial cross-linking study, showing that a range of pore proteins can be crosslinked by formaldehyde to many genes, among which are those induced by galactose.

    CAS  PubMed  Google Scholar 

  3. Chen, L. Co-inhibitory molecules of the B7–CD28 family in the control of T-cell immunity. Nat. Rev. Immunol. 4, 336–347 (2004).

    CAS  PubMed  Google Scholar 

  4. Nakae, S. et al. Mast cells enhance T cell activation: importance of mast cell costimulatory molecules and secreted TNF. J. Immunol. 176, 2238–2248 (2006).

    CAS  PubMed  Google Scholar 

  5. Latchman, Y. et al. PD-L2 is a second ligand for PD-1 and inhibits T cell activation. Nat. Immunol. 2, 261–268 (2001).This paper uses a technique involving the fusion of a pore protein to MN to show that promoters associate with nuclear pores in yeast.

    CAS  PubMed  Google Scholar 

  6. Augello, A. et al. Bone marrow mesenchymal progenitor cells inhibit lymphocyte proliferation by activation of the programmed death 1 pathway. Eur. J. Immunol. 35, 1482–1490 (2005).

    CAS  PubMed  Google Scholar 

  7. Brown, J.A. et al. Blockade of programmed death-1 ligands on dendritic cells enhances T cell activation and cytokine production. J. Immunol. 170, 1257–1266 (2003).

    CAS  PubMed  Google Scholar 

  8. Rodig, N. et al. Endothelial expression of PD-L1 and PD-L2 down-regulates CD8+ T cell activation and cytolysis. Eur. J. Immunol. 33, 3117–3126 (2003).

    CAS  PubMed  Google Scholar 

  9. Eppihimer, M.J. et al. Expression and regulation of the PD-L1 immunoinhibitory molecule on microvascular endothelial cells. Microcirculation 9, 133–145 (2002).

    CAS  PubMed  PubMed Central  Google Scholar 

  10. Muhlbauer, M. et al. PD-L1 is induced in hepatocytes by viral infection and by interferon-α and -γ and mediates T cell apoptosis. J. Hepatol. 45, 520–528 (2006).

    PubMed  Google Scholar 

  11. Selenko-Gebauer, N. et al. B7-H1 (programmed death-1 ligand) on dendritic cells is involved in the induction and maintenance of T cell anergy. J. Immunol. 170, 3637–3644 (2003).

    CAS  PubMed  Google Scholar 

  12. Barber, D.L. et al. Restoring function in exhausted CD8 T cells during chronic viral infection. Nature 439, 682–687 (2006).

    CAS  PubMed  Google Scholar 

  13. Koga, N. et al. Blockade of the interaction between PD-1 and PD-L1 accelerates graft arterial disease in cardiac allografts. Arterioscler. Thromb. Vasc. Biol. 24, 2057–2062 (2004).

    CAS  PubMed  Google Scholar 

  14. Parry, R.V. et al. CTLA-4 and PD-1 receptors inhibit T-cell activation by distinct mechanisms. Mol. Cell. Biol. 25, 9543–9553 (2005).

    CAS  PubMed  PubMed Central  Google Scholar 

  15. Freeman, G.J. et al. Engagement of the PD-1 immunoinhibitory receptor by a novel B7 family member leads to negative regulation of lymphocyte activation. J. Exp. Med. 192, 1027–1034 (2000).

    CAS  PubMed  PubMed Central  Google Scholar 

  16. Dong, H., Zhu, G., Tamada, K. & Chen, L. B7-H1, a third member of the B7 family, costimulates T-cell proliferation and interleukin-10 secretion. Nat. Med. 5, 1365–1369 (1999).

    CAS  PubMed  Google Scholar 

  17. Tseng, S.Y. et al. B7-DC, a new dendritic cell molecule with potent costimulatory properties for T cells. J. Exp. Med. 193, 839–846 (2001).

    CAS  PubMed  PubMed Central  Google Scholar 

  18. 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 11, 141–151 (1999).

    CAS  PubMed  Google Scholar 

  19. Latchman, Y.E. et al. PD-L1-deficient mice show that PD-L1 on T cells, antigenpresenting cells, and host tissues negatively regulates T cells. Proc. Natl. Acad. Sci. USA 101, 10691–10696 (2004).

    CAS  PubMed  Google Scholar 

  20. Keir, M.E. et al. Tissue expression of PD-L1 mediates peripheral T cell tolerance. J. Exp. Med. 203, 883–895 (2006).

    CAS  PubMed  PubMed Central  Google Scholar 

  21. Dong, H. et al. B7–H1 determines accumulation and deletion of intrahepatic CD8+ T lymphocytes. Immunity 20, 327–336 (2004).

    CAS  PubMed  Google Scholar 

  22. Kuipers, H. et al. Contribution of the PD-1 ligands/PD-1 signaling pathway to dendritic cell-mediated CD4+ T cell activation. Eur. J. Immunol. 36, 2472–2482 (2006).

    CAS  PubMed  Google Scholar 

  23. Blocki, F.A. et al. Induction of a gene expression program in dendritic cells with a crosslinking IgM antibody to the co-stimulatory molecule B7-DC. FASEB J. 20, 2408–2410 (2006).

    CAS  PubMed  Google Scholar 

  24. Van Keulen, V.P. et al. Immunomodulation using the recombinant monoclonal human B7-DC cross-linking antibody rHIgM12. Clin. Exp. Immunol. 143, 314–321 (2006).

    CAS  PubMed  PubMed Central  Google Scholar 

  25. Liang, S.C. et al. Regulation of PD-1, PD-L1, and PD-L2 expression during normal and autoimmune responses. Eur. J. Immunol. 33, 2706–2716 (2003).

    CAS  PubMed  Google Scholar 

  26. 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. 191, 891–898 (2000).

    CAS  PubMed  PubMed Central  Google Scholar 

  27. Keir, M.E., Latchman, Y.E., Freeman, G.J. & Sharpe, A.H. Programmed death-1 (PD- 1):PD-ligand 1 interactions inhibit TCR-mediated positive selection of thymocytes. J. Immunol. 175, 7372–7379 (2005).

    CAS  PubMed  PubMed Central  Google Scholar 

  28. Blank, C. et al. Absence of programmed death receptor 1 alters thymic development and enhances generation of CD4/CD8 double-negative TCR-transgenic T cells. J. Immunol. 171, 4574–4581 (2003).

    CAS  PubMed  Google Scholar 

  29. Nishimura, H. et al. Autoimmune dilated cardiomyopathy in PD-1 receptor-deficient mice. Science 291, 319–322 (2001).

    CAS  PubMed  Google Scholar 

  30. Sabapatha, A., Gercel-Taylor, C. & Taylor, D.D. Specific isolation of placenta-derived exosomes from the circulation of pregnant women and their immunoregulatory consequences. Am. J. Reprod. Immunol. 56, 345–355 (2006).

    CAS  PubMed  Google Scholar 

  31. Holets, L.M., Hunt, J.S. & Petroff, M.G. Trophoblast CD274 (B7-H1) is differentially expressed across gestation: influence of oxygen concentration. Biol. Reprod. 74, 352–358 (2006).

    CAS  PubMed  Google Scholar 

  32. Guleria, I. et al. A critical role for the programmed death ligand 1 in fetomaternal tolerance. J. Exp. Med. 202, 231–237 (2005).

    CAS  PubMed  PubMed Central  Google Scholar 

  33. Hori, J. et al. B7-H1-induced apoptosis as a mechanism of immune privilege of corneal allografts. J. Immunol. 177, 5928–5935 (2006).

    CAS  PubMed  Google Scholar 

  34. Meng, Q. et al. CD4+PD-1+ T cells acting as regulatory cells during the induction of anterior chamber-associated immune deviation. Invest. Ophthalmol. Vis. Sci. 47, 4444–4452 (2006).

    PubMed  Google Scholar 

  35. Watson, M.P., George, A.J. & Larkin, D.F. Differential effects of costimulatory pathway modulation on corneal allograft survival. Invest. Ophthalmol. Vis. Sci. 47, 3417–3422 (2006).

    PubMed  Google Scholar 

  36. Probst, H.C., 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. 6, 280–286 (2005).

    CAS  PubMed  Google Scholar 

  37. Hirata, S. et al. Prevention of experimental autoimmune encephalomyelitis by transfer of embryonic stem cell-derived dendritic cells expressing myelin oligodendrocyte glycoprotein peptide along with TRAIL or programmed death-1 ligand. J. Immunol. 174, 1888–1897 (2005).

    CAS  PubMed  Google Scholar 

  38. Wang, J. et al. Establishment of NOD-Pdcd1−/− mice as an efficient animal model of type I diabetes. Proc. Natl. Acad. Sci. USA 102, 11823–11828 (2005).

    CAS  PubMed  Google Scholar 

  39. Ansari, M.J. et al. The programmed death-1 (PD-1) pathway regulates autoimmune diabetes in nonobese diabetic (NOD) mice. J. Exp. Med. 198, 63–69 (2003).

    CAS  PubMed  PubMed Central  Google Scholar 

  40. Fife, B.T. et al. Insulin-induced remission in new-onset NOD mice is maintained by the PD-1-PD-L1 pathway. J. Exp. Med. 203, 2737–2747 (2006).

    CAS  PubMed  PubMed Central  Google Scholar 

  41. Salama, A.D. et al. Critical role of the programmed death-1 (PD-1) pathway in regulation of experimental autoimmune encephalomyelitis. J. Exp. Med. 198, 71–78 (2003).

    CAS  PubMed  PubMed Central  Google Scholar 

  42. Zhu, B. et al. Differential role of programmed death-ligand 1 and programmed death-ligand 2 in regulating the susceptibility and chronic progression of experimental autoimmune encephalomyelitis. J. Immunol. 176, 3480–3489 (2006).

    CAS  PubMed  Google Scholar 

  43. Zhang, Y. et al. Regulation of T cell activation and tolerance by PDL2. Proc. Natl. Acad. Sci. USA 103, 11695–11700 (2006).

    CAS  PubMed  Google Scholar 

  44. Schreiner, B. et al. Interferon-beta enhances monocyte and dendritic cell expression of B7-H1 (PD-L1), a strong inhibitor of autologous T-cell activation: relevance for the immune modulatory effect in multiple sclerosis. J. Neuroimmunol. 155, 172–182 (2004).

    CAS  PubMed  Google Scholar 

  45. Dong, H. et al. Costimulating aberrant T cell responses by B7-H1 autoantibodies in rheumatoid arthritis. J. Clin. Invest. 111, 363–370 (2003).

    CAS  PubMed  PubMed Central  Google Scholar 

  46. Isogawa, M., Furuichi, Y. & Chisari, F.V. Oscillating CD8+ T cell effector functions after antigen recognition in the liver. Immunity 23, 53–63 (2005).

    CAS  PubMed  Google Scholar 

  47. 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. 198, 39–50 (2003).

    CAS  PubMed  PubMed Central  Google Scholar 

  48. Kaech, S.M., Wherry, E.J. & Ahmed, R. Effector and memory T-cell differentiation: implications for vaccine development. Nat. Rev. Immunol. 2, 251–262 (2002).

    CAS  PubMed  Google Scholar 

  49. Wherry, E.J., Blattman, J.N. & Ahmed, R. Low CD8 T-cell proliferative potential and high viral load limit the effectiveness of therapeutic vaccination. J. Virol. 79, 8960–8968 (2005).

    CAS  PubMed  PubMed Central  Google Scholar 

  50. Wherry, E.J. & Ahmed, R. Memory CD8 T-cell differentiation during viral infection. J. Virol. 78, 5535–5545 (2004).

    CAS  PubMed  PubMed Central  Google Scholar 

  51. Wherry, E.J., Blattman, J.N., Murali-Krishna, K., van der Most, R. & Ahmed, R. Viral persistence alters CD8 T-cell immunodominance and tissue distribution and results in distinct stages of functional impairment. J. Virol. 77, 4911–4927 (2003).

    CAS  PubMed  PubMed Central  Google Scholar 

  52. Betts, M.R. et al. Characterization of functional and phenotypic changes in anti-Gag vaccine-induced T cell responses and their role in protection after HIV-1 infection. Proc. Natl. Acad. Sci. USA 102, 4512–4517 (2005).

    CAS  PubMed  Google Scholar 

  53. Betts, M.R. et al. HIV nonprogressors preferentially maintain highly functional HIV-specific CD8+ T cells. Blood 107, 4781–4789 (2006).

    CAS  PubMed  PubMed Central  Google Scholar 

  54. Klenerman, P. & Hill, A. T cells and viral persistence: lessons from diverse infections. Nat. Immunol. 6, 873–879 (2005).

    CAS  PubMed  Google Scholar 

  55. Day, C.L. et al. PD-1 expression on HIV-specific T cells is associated with T-cell exhaustion and disease progression. Nature 443, 350–354 (2006).

    CAS  PubMed  Google Scholar 

  56. Petrovas, C. et al. PD-1 is a regulator of virus-specific CD8+ T cell survival in HIV infection. J. Exp. Med. 203, 2281–2292 (2006).

    CAS  PubMed  PubMed Central  Google Scholar 

  57. Trautmann, L. et al. Upregulation of PD-1 expression on HIV-specific CD8+ T cells leads to reversible immune dysfunction. Nat. Med. 12, 1198–1202 (2006).

    CAS  PubMed  Google Scholar 

  58. Boettler, T. et al. Expression of the interleukin-7 receptor α chain (CD127) on virus-specific CD8+ T cells identifies functionally and phenotypically defined memory T cells during acute resolving hepatitis B virus infection. J. Virol. 80, 3532–3540 (2006).

    CAS  PubMed  PubMed Central  Google Scholar 

  59. Urbani, S. et al. PD-1 expression in acute hepatitis C virus (HCV) infection is associated with HCV-specific CD8 exhaustion. J. Virol. 80, 11398–11403 (2006).

    CAS  PubMed  PubMed Central  Google Scholar 

  60. Kirchberger, S. et al. Human rhinoviruses inhibit the accessory function of dendritic cells by inducing sialoadhesin and B7-H1 expression. J. Immunol. 175, 1145–1152 (2005).

    CAS  PubMed  Google Scholar 

  61. Jun, H. et al. B7-H1 (CD274) inhibits the development of herpetic stromal keratitis (HSK). FEBS Lett. 579, 6259–6264 (2005).

    CAS  PubMed  Google Scholar 

  62. Stanciu, L.A. et al. Expression of programmed death-1 ligand (PD-L) 1, PD-L2, B7-H3, and inducible costimulator ligand on human respiratory tract epithelial cells and regulation by respiratory syncytial virus and type 1 and 2 cytokines. J. Infect. Dis. 193, 404–412 (2006).

    PubMed  Google Scholar 

  63. Chang, J. & Braciale, T.J. Respiratory syncytial virus infection suppresses lung CD8+ Tcell effector activity and peripheral CD8+ T-cell memory in the respiratory tract. Nat. Med. 8, 54–60 (2002).

    CAS  PubMed  Google Scholar 

  64. Anderson, K.M., Czinn, S.J., Redline, R.W. & Blanchard, T.G. Induction of CTLA-4-mediated anergy contributes to persistent colonization in the murine model of gastric Helicobacter pylori infection. J. Immunol. 176, 5306–5313 (2006).

    CAS  PubMed  Google Scholar 

  65. Stromberg, E. et al. Increased frequency of activated T-cells in the Helicobacter pylori-infected antrum and duodenum. FEMS Immunol. Med. Microbiol. 36, 159–168 (2003).

    CAS  PubMed  Google Scholar 

  66. Das, S. et al. Expression of B7–H1 on gastric epithelial cells: its potential role in regulating T cells during Helicobacter pylori infection. J. Immunol. 176, 3000–3009 (2006).

    CAS  PubMed  Google Scholar 

  67. Cohen, N., Morisset, J. & Emilie, D. Induction of tolerance by Porphyromonas gingivalis on APCS: a mechanism implicated in periodontal infection. J. Dent. Res. 83, 429–433 (2004).

    CAS  PubMed  Google Scholar 

  68. Kamradt, T. T cell unresponsiveness in lepromatous leprosy. J. Rheumatol. 20, 904–906 (1993).

    CAS  PubMed  Google Scholar 

  69. Kaufmann, S.H. Tuberculosis: back on the immunologists' agenda. Immunity 24, 351–357 (2006).

    CAS  PubMed  Google Scholar 

  70. Loomis, W.P. & Starnbach, M.N. Chlamydia trachomatis infection alters the development of memory CD8+ T cells. J. Immunol. 177, 4021–4027 (2006).

    CAS  PubMed  Google Scholar 

  71. Smith, P. et al. Schistosoma mansoni worms induce anergy of T cells via selective upregulation of programmed death ligand 1 on macrophages. J. Immunol. 173, 1240–1248 (2004).

    CAS  PubMed  Google Scholar 

  72. Terrazas, L.I., Montero, D., Terrazas, C.A., Reyes, J.L. & Rodriguez-Sosa, M. Role of the programmed death-1 pathway in the suppressive activity of alternatively activated macrophages in experimental cysticercosis. Int. J. Parasitol. 35, 1349–1358 (2005).

    CAS  PubMed  Google Scholar 

  73. Liang, S.C. et al. PD-L1 and PD-L2 have distinct roles in regulating host immunity to cutaneous leishmaniasis. Eur. J. Immunol. 36, 58–64 (2006).

    CAS  PubMed  Google Scholar 

  74. Kroner, A. et al. A PD-1 polymorphism is associated with disease progression in multiple sclerosis. Ann. Neurol. 58, 50–57 (2005).

    CAS  PubMed  Google Scholar 

  75. Nielsen, C. et al. A putative regulatory polymorphism in PD-1 is associated with nephropathy in a population-based cohort of systemic lupus erythematosus patients. Lupus 13, 510–516 (2004).

    CAS  PubMed  Google Scholar 

  76. Nielsen, C., Hansen, D., Husby, S., Jacobsen, B.B. & Lillevang, S.T. Association of a putative regulatory polymorphism in the PD-1 gene with susceptibility to type 1 diabetes. Tissue Antigens 62, 492–497 (2003).

    CAS  PubMed  Google Scholar 

  77. Kong, E.K. et al. A new haplotype of PDCD1 is associated with rheumatoid arthritis in Hong Kong Chinese. Arthritis Rheum. 52, 1058–1062 (2005).

    CAS  PubMed  Google Scholar 

  78. Prokunina, L. et al. A regulatory polymorphism in PDCD1 is associated with susceptibility to systemic lupus erythematosus in humans. Nat. Genet. 32, 666–669 (2002).

    CAS  PubMed  Google Scholar 

  79. Lin, S.C. et al. Association of a programmed death 1 gene polymorphism with the development of rheumatoid arthritis, but not systemic lupus erythematosus. Arthritis Rheum. 50, 770–775 (2004).

    CAS  PubMed  Google Scholar 

  80. Johansson, M., Arlestig, L., Moller, B. & Rantapaa-Dahlqvist, S. Association of a PDCD1 polymorphism with renal manifestations in systemic lupus erythematosus. Arthritis Rheum. 52, 1665–1669 (2005).

    CAS  PubMed  Google Scholar 

  81. Prokunina, L. et al. Association of the PD-1.3A allele of the PDCD1 gene in patients with rheumatoid arthritis negative for rheumatoid factor and the shared epitope. Arthritis Rheum. 50, 1770–1773 (2004).

    CAS  PubMed  Google Scholar 

  82. Wang, S.C. et al. Programmed death-1 gene polymorphisms in patients with systemic lupus erythematosus in taiwan. J. Clin. Immunol. 26, 506–511 (2006).

    PubMed  Google Scholar 

  83. Lee, S.H. et al. Association of the programmed cell death 1 (PDCD1) gene polymorphism with ankylosing spondylitis in the Korean population. Arthritis Res. Ther. 8, R163 (2006).

    PubMed  PubMed Central  Google Scholar 

  84. Ferreiros-Vidal, I. et al. Association of PDCD1 with susceptibility to systemic lupus erythematosus: evidence of population-specific effects. Arthritis Rheum. 50, 2590–2597 (2004).

    CAS  PubMed  Google Scholar 

  85. James, E.S. et al. PDCD1: a tissue-specific susceptibility locus for inherited inflammatory disorders. Genes Immun. 6, 430–437 (2005).

    CAS  PubMed  Google Scholar 

  86. Sigal, L.H. Lyme disease: a review of aspects of its immunology and immunopathogenesis. Annu. Rev. Immunol. 15, 63–92 (1997).

    CAS  PubMed  Google Scholar 

  87. Huber, S.A. Autoimmunity in coxsackievirus B3 induced myocarditis. Autoimmunity 39, 55–61 (2006).

    CAS  PubMed  Google Scholar 

  88. Sawada, S. & Takei, M. Epstein-Barr virus etiology in rheumatoid synovitis. Autoimmun. Rev. 4, 106–110 (2005).

    CAS  PubMed  Google Scholar 

  89. Daniel-Ribeiro, C.T. & Zanini, G. Autoimmunity and malaria: what are they doing together? Acta Trop. 76, 205–221 (2000).

    CAS  PubMed  Google Scholar 

  90. Zaccone, P., Fehervari, Z., Phillips, J.M., Dunne, D.W. & Cooke, A. Parasitic worms and inflammatory diseases. Parasite Immunol. 28, 515–523 (2006).

    CAS  PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgements

Supported by the National Institutes of Health, the National Multiple Sclerosis Society and the Foundation for the National Institutes of Health through the Grand Challenges in Global Health Initiative.

Author information

Authors and Affiliations

  1. Department of Pathology, Harvard Medical School and Brigham and Women's Hospital, Boston, 02115, Massachusetts, USA

    Arlene H Sharpe

  2. Immunology Program, The Wistar Institute, Philadelphia, 19104, Pennsylvania, USA

    E John Wherry

  3. Emory Vaccine Center and Department of Microbiology and Immunology, Emory University School of Medicine, Atlanta, 30322, Georgia, USA

    Rafi Ahmed

  4. Department of Medical Oncology, Department of Medicine, Dana-Farber Cancer Institute, Harvard Medical School, Boston, 02115, Massachusetts, USA

    Gordon J Freeman

Authors
  1. Arlene H Sharpe
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. E John Wherry
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Rafi Ahmed
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Gordon J Freeman
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Arlene H Sharpe.

Ethics declarations

Competing interests

The authors declare no competing financial interests.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Sharpe, A., Wherry, E., Ahmed, R. et al. The function of programmed cell death 1 and its ligands in regulating autoimmunity and infection. Nat Immunol 8, 239–245 (2007). https://doi.org/10.1038/ni1443

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/ni1443

This article is cited by

Search

Advanced search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing