PD-1 and CTLA-4 inhibitory cosignaling pathways in HIV infection and the potential for therapeutic intervention

Journal of Immunology

Volumn 182, Issue 10, 2009, Pages 5891-5897

  Kaufmann, Daniel E ^a   Walker, Bruce D ^a,b  

^a MASSACHUSETTS INSTITUTE OF TECHNOLOGY   (United States)

^b HOWARD HUGHES MEDICAL INSTITUTE   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

ALPHA INTERFERON; B7 ANTIGEN; CD28 ANTIGEN; CD4 ANTIGEN; CD8 ANTIGEN; CD83 ANTIGEN; CD86 ANTIGEN; CYTOTOXIC T LYMPHOCYTE ANTIGEN 4; FAS ANTIBODY; INTERLEUKIN 10; INTERLEUKIN 15; INTERLEUKIN 2; INTERLEUKIN 21; INTERLEUKIN 7; MAJOR HISTOCOMPATIBILITY ANTIGEN; NEF PROTEIN; NUCLEOPHOSMIN; TOLL LIKE RECEPTOR;

APOPTOSIS; AUTOIMMUNE DISEASE; AUTOIMMUNITY; B LYMPHOCYTE; CANCER CELL; CD4 LYMPHOCYTE COUNT; CD4+ T LYMPHOCYTE; CD8+ T LYMPHOCYTE; CELL FUNCTION; CELL MOTILITY; CELL STIMULATION; COLITIS; CYTOKINE RELEASE; DENDRITIC CELL; DISEASE COURSE; DNA POLYMORPHISM; DOWN REGULATION; EPSTEIN BARR VIRUS; HELICOBACTER PYLORI; HEPATITIS B VIRUS; HUMAN; HUMAN IMMUNODEFICIENCY VIRUS INFECTION; HYPOPHYSITIS; IMMUNE RESPONSE; IMMUNOPATHOLOGY; IN VITRO STUDY; IN VIVO STUDY; INFECTION; INFLAMMATION; INTESTINE LYMPHATIC TISSUE; LEISHMANIA; LYMPHOCYTIC CHORIOMENINGITIS VIRUS; LYMPHOID ORGAN; LYMPHOMA CELL LINE; MONOCYTE; NONHUMAN; PERIPHERAL BLOOD MONONUCLEAR CELL; PRIORITY JOURNAL; REVIEW; SCHISTOSOMIASIS MANSONI; SIMIAN IMMUNODEFICIENCY VIRUS; SPLEEN CELL; T LYMPHOCYTE; T LYMPHOCYTE ACTIVATION; TRYPANOSOMA; UPREGULATION; VIREMIA; VIRUS LOAD;

ANIMALS; ANTIGENS, CD; APOPTOSIS REGULATORY PROTEINS; CD4-POSITIVE T-LYMPHOCYTES; HIV INFECTIONS; HUMANS; SIGNAL TRANSDUCTION; SIMIAN IMMUNODEFICIENCY VIRUS;

EID: 70350743827     PISSN: 00221767     EISSN: 15506606     Source Type: Journal    
DOI: 10.4049/jimmunol.0803771     Document Type: Review

References (70)

1. Deeks, S. G., and B. D. Walker. 2007. Human immunodeficiency virus controllers: mechanisms of durable virus control in the absence of antiretroviral therapy. Immunity 27: 406-416.
2. Zajac, A. J., J. N. Blattman, K. Murali-Krishna, D. J. Sourdive, M. Suresh, J. D. Altman, and R. Ahmed. 1998. Viral immune evasion due to persistence of activated T cells without effector function [see comments]. J. Exp. Med. 188: 2205-2213.
3. + T cell exhaustion during chronic viral infection. Immunity 27: 670-684.
4. Haining, W. N., B. L. Ebert, A. Subrmanian, E. J. Wherry, Q. Eichbaum, J. W. Evans, R. Mak, S. Rivoli, J. Pretz, J. Angelosanto, et al. 2008. Identification of an evolutionarily conserved transcriptional signature of CD8 memory differentiation that is shared by T and B cells. J. Immunol. 181: 1859-1868.
5. Greenwald, R. J., G. J. Freeman, and A. H. Sharpe. 2005. The B7 family revisited. Annu. Rev. Immunol. 23: 515-548.
6. Chen, L. 2004. Co-inhibitory molecules of the B7-CD28 family in the control of T-cell immunity. Nat. Rev. Immunol. 4: 336-347.
7. Teft, W. A., M. G. Kirchhof, and J. Madrenas. 2006. A molecular Perspective of Ctla-4 Function. Annu. Rev. Immunol. 24: 65-97.
8. Hodi, F. S., M. C. Mihm, R. J. Soiffer, F. G. Haluska, M. Butler, M. V. Seiden, T. Davis, R. Henry-Spires, S. MacRae, A. Willman, et al. 2003. Biologic activity of cytotoxic T lymphocyte-associated antigen 4 antibody blockade in previously vaccinated metastatic melanoma and ovarian carcinoma patients. Proc. Natl. Acad. Sci. USA 100: 4712-4717.
9. Phan, G. Q., J. C. Yang, R. M. Sherry, P. Hwu, S. L. Topalian, D. J. Schwartzentruber, N. P. Restifo, L. R. Haworth, C. A. Seipp, L. J. Freezer, et al. 2003. Cancer regression and autoimmunity induced by cytotoxic T lymphocyte-associated antigen 4 blockade in patients with metastatic melanoma. Proc. Natl. Acad. Sci. USA 100: 8372-8377.
10. Fife, B. T., and J. A. Bluestone. 2008. Control of peripheral T-cell tolerance and autoimmunity via the CTLA-4 and PD-1 pathways. Immunol. Rev. 224: 166-182.
11. Parry, R. V., J. M. Chemnitz, K. A. Frauwirth, A. R. Lanfranco, I. Braunstein, S. V. Kobayashi, P. S. Linsley, C. B. Thompson, and J. L. Riley. 2005. CTLA-4 and PD-1 receptors inhibit T-cell activation by distinct mechanisms. Mol. Cell. Biol. 25: 9543-9553.
12. + T cell survival in HIV infection. J. Exp. Med. 203: 2281-2292.
13. Blackburn, S. D., H. Shin, G. J. Freeman, and E. J. Wherry. 2008. Selective expansion of a subset of exhausted CD8 T cells by αPD-L1 blockade. Proc. Natl. Acad. Sci. USA 105: 15016-15021.
14. Schneider, H., J. Downey, A. Smith, B. H. Zinselmeyer, C. Rush, J. M. Brewer, B. Wei, N. Hogg, P. Garside, and C. E. Rudd. 2006. Reversal of the TCR stop signal by CTLA-4. Science 313: 1972-1975.
15. + regulatory T cell function. Science 322: 271-275.
16. + regulatory T cells require CTLA-4 for the maintenance of systemic tolerance. J. Exp. Med. 206: 421-434.
17. Butte, M. J., M. E. Keir, T. B. Phamduy, A. H. Sharpe, and G. J. Freeman. 2007. Programmed death-1 ligand 1 interacts specifically with the B7-1 costimulatory molecule to inhibit T cell responses. Immunity 27: 111-122.
18. Barber, D. L., E. J. Wherry, D. Masopust, B. Zhu, J. P. Allison, A. H. Sharpe, G. J. Freeman, and R. Ahmed. 2006. Restoring function in exhausted CD8 T cells during chronic viral infection. Nature 439: 682-687.
19. Ha, S. J., S. N. Mueller, E. J. Wherry, D. L. Barber, R. D. Aubert, A. H. Sharpe, G. J. Freeman, and R. Ahmed. 2008. Enhancing therapeutic vaccination by blocking PD-1-mediated inhibitory signals during chronic infection. J. Exp. Med. 205: 543-555.
20. Day, C. L., D. E. Kaufmann, P. Kiepiela, J. A. Brown, E. S. Moodley, S. Reddy, E. W. Mackey, J. D. Miller, A. J. Leslie, C. DePierres, et al. 2006. PD-1 expression on HIV-specific T cells is associated with T-cell exhaustion and disease progression. Nature 443: 350-354.
21. + T cells leads to reversible immune dysfunction. Nat. Med. 12: 1198-1202.
22. + T cell exhaustion by multiple inhibitory receptors during chronic viral infection. Nat. Immunol. 10: 29-37.
23. + T cells: constitutive up-regulation in controllers and selective increase by blockade of PD ligand 1 in progressors. Blood 112: 3679-3687.
24. + T cells. PLoS Med. 5: e100.
25. Muthumani, K., A. Y. Choo, D. J. Shedlock, D. J. Laddy, S. G. Sundaram, L. Hirao, L. Wu, K. P. Thieu, C. W. Chung, K. M. Lankaraman, et al. 2008. Human immunodeficiency virus type 1 Nef induces programmed death 1 expression through a p38 mitogen-activated protein kinase-dependent mechanism. J. Virol. 82: 11536-11544.
26. Kinter, A. L., E. J. Godbout, J. P. McNally, I. Sereti, G. A. Roby, M. A. O'Shea, and A. S. Fauci. 2008. The common γ-chain cytokines IL-2, IL-7, IL-15, and IL-21 induce the expression of programmed death-1 and its ligands. J. Immunol. 181: 6738-6746.
27. + T cells is driven by viral replication and associated with T cell dysfunction. J. Immunol. 179: 1979-1987.
28. Oestreich, K. J., H. Yoon, R. Ahmed, and J. M. Boss. 2008. NFATc1 regulates PD-1 expression upon T cell activation. J. Immunol. 181: 4832-4839.
29. + T lymphocytes are prognostic factors of human ovarian cancer. Proc. Natl. Acad. Sci. USA 104: 3360-3365.
30. Smith, P., C. M. Walsh, N. E. Mangan, R. E. Fallon, J. R. Sayers, A. N. McKenzie, and P. G. Fallon. 2004. Schistosoma mansoni worms induce anergy of T cells via selective up-regulation of programmed death ligand 1 on macrophages. J. Immunol. 173: 1240-1248.
31. Mueller, S. N., M. Matloubian, D. M. Clemens, A. H. Sharpe, G. J. Freeman, S. Gangappa, C. P. Larsen, and R. Ahmed. 2007. Viral targeting of fibroblastic reticular cells contributes to immunosuppression and persistence during chronic infection. Proc. Natl. Acad. Sci. USA 104: 15430-15435.
32. Trabattoni, D., M. Saresella, M. Biasin, A. Boasso, L. Piacentini, P. Ferrante, H. Dong, R. Maserati, G. M. Shearer, L. Chen, and M. Clerici. 2003. B7-H1 is upregulated in HIV infection and is a novel surrogate marker of disease progression. Blood 101: 2514-2520.
33. Wang, X., Z. Zhang, S. Zhang, J. Fu, J. Yao, Y. Jiao, H. Wu, and F. S. Wang. 2008. B7-H1 up-regulation impairs myeloid DC and correlates with disease progression in chronic HIV-1 infection. Eur. J. Immunol. 38: 3226-3236.
34. Boasso, A., A. W. Hardy, A. L. Landay, J. L. Martinson, S. A. Anderson, M. J. Dolan, M. Clerici, and G. M. Shearer. 2008. PDL-1 upregulation on monocytes and T cells by HIV via type I interferon: restricted expression of type I interferon receptor by CCR5-expressing leukocytes. Clin. Immunol. 129: 132-144.
35. Meier, A., A. Bagchi, H. K. Sidhu, G. Alter, T. J. Suscovich, D. G. Kavanagh, H. Streeck, M. A. Brockman, S. LeGall, J. Hellman, and M. Altfeld. 2008. Upregulation of PD-L1 on monocytes and dendritic cells by HIV-1 derived TLR ligands. AIDS 22: 655-658.
36. Marzec, M., Q. Zhang, A. Goradia, P. N. Raghunath, X. Liu, M. Paessler, H. Y. Wang, M. Wysocka, M. Cheng, B. A. Ruggeri, and M. A. Wasik. 2008. Oncogenic kinase NPM/ALK induces through STAT3 expression of immunosuppressive protein CD274 (PD-L1, B7-H1). Proc. Natl. Acad. Sci. USA 105: 20852-20857.
37. Leach, D. R., M. F. Krummel, and J. P. Allison. 1996. Enhancement of antitumor immunity by CTLA-4 blockade. Science 271: 1734-1736.
38. Anderson, K. M., S. J. Czinn, R. W. Redline, and T. G. Blanchard. 2006. Induction of CTLA-4-mediated anergy contributes to persistent colonization in the murine model of gastric Helicobacter pylori infection. J. Immunol. 176: 5306-5313.
39. Zubairi, S., S. L. Sanos, S. Hill, and P. M. Kaye. 2004. Immunotherapy with OX40L-Fc or anti-CTLA-4 enhances local tissue responses and killing of Leishmania donovani. Eur. J. Immunol. 34: 1433-1440.
40. Gomes, N. A., C. R. Gattass, V. Barreto-De-Souza, M. E. Wilson, and G. A. DosReis. 2000. TGF-β mediates CTLA-4 suppression of cellular immunity in murine kalaazar. J. Immunol. 164: 2001-2008.
41. Graefe, S. E., T. Jacobs, U. Wachter, B. M. Broker, and B. Fleischer. 2004. CTLA-4 regulates the murine immune response to Trypanosoma cruzi infection. Parasite Immunol. 26: 19-28.
42. Thio, C. L., T. L. Mosbruger, R. A. Kaslow, C. L. Karp, S. A. Strathdee, D. Vlahov, S. J. O'Brien, J. Astemborski, and D. L. Thomas. 2004. Cytotoxic T-lymphocyte antigen 4 gene and recovery from hepatitis B virus infection. J. Virol. 78: 11258-11262.
43. Leng, Q., Z. Bentwich, E. Magen, A. Kalinkovich, and G. Borkow. 2002. CTLA-4 upregulation during HIV infection: association with anergy and possible target for therapeutic intervention. AIDS 16: 519-529.
44. + cells and overexpression of CTLA-4 are linked to loss of antigen-specific CD4 T cells during primary human immunodeficiency virus type 1 infection. J. Virol. 80: 10162-10172.
45. + T cells correlates with disease progression and defines a reversible immune dysfunction. Nat. Immunol. 8: 1246-1254.
46. + T cells. Science 276: 273-276.
47. Riley, J. L., K. Schlienger, P. J. Blair, B. Carreno, N. Craighead, D. Kim, R. G. Carroll, and C. H. June. 2000. Modulation of susceptibility to HIV-1 infection by the cytotoxic T lymphocyte antigen 4 costimulatory molecule. J. Exp. Med. 191: 1987-1997.
48. Hardy, A. W., D. R. Graham, G. M. Shearer, and J. P. Herbeuval. 2007. HIV turns plasmacytoid dendritic cells (pDC) into TRAIL-expressing killer pDC and down-regulates HIV coreceptors by Toll-like receptor 7-induced IFN-α. Proc. Natl. Acad. Sci. USA 104: 17453-17458.
49. Yonezawa, A., R. Morita, A. Takaori-Kondo, N. Kadowaki, T. Kitawaki, T. Hori, and T. Uchiyama. 2003. Natural alpha interferon-producing cells respond to human immunodeficiency virus type 1 with alpha interferon production and maturation into dendritic cells. J. Virol. 77: 3777-3784.
50. + dendritic cells with reduced CD80 and CD86 expression in lymphoid tissue during acute HIV-1 infection. AIDS 16: 683-692.
51. Malaspina, A., S. Moir, S. Kottilil, C. W. Hallahan, L. A. Ehler, S. Liu, M. A. Planta, T. W. Chun, and A. S. Fauci. 2003. Deleterious effect of HIV-1 plasma viremia on B cell costimulatory function. J. Immunol. 170: 5965-5972.
52. Kochli, C., T. Wendland, K. Frutig, R. Grunow, S. Merlin, and W. J. Pichler. 1999. CD80 and CD86 costimulatory molecules on circulating T cells of HIV infected individuals. Immunol. Lett. 65: 197-201.
53. + T cells express high levels of PD1 and cytokines but have impaired proliferative capacity in acute and chronic SIVmac251 infection. Blood 110: 928-936.
54. Velu, V., S. Kannanganat, C. Ibegbu, L. Chennareddi, F. Villinger, G. J. Freeman, R. Ahmed, and R. R. Amara. 2007. Elevated expression levels of inhibitory receptor programmed death 1 on simian immunodeficiency virus-specific CD8 T cells during chronic infection but not after vaccination. J. Virol. 81: 5819-5828.
55. Estes, J. D., S. N. Gordon, M. Zeng, A. M. Chahroudi, R. M. Dunham, S. I. Staprans, C. S. Reilly, G. Silvestri, and A. T. Haase. 2008. Early resolution of acute immune activation and induction of PD-1 in SIV-infected sooty mangabeys distinguishes nonpathogenic from pathogenic infection in rhesus macaques. J. Immunol. 180: 6798-6807.
56. Velu, V., K. Titanji, B. Zhu, S. Husain, A. Pladevega, L. Lai, T. H. Vanderford, L. Chennareddi, G. Silvestri, G. J. Freeman, et al. 2009. Enhancing SIV-specific immunity in vivo by PD-1 blockade. Nature 458: 206-210.
57. Boasso, A., M. Vaccari, A. Hryniewicz, D. Fuchs, J. Nacsa, V. Cecchinato, J. Andersson, G. Franchini, G. M. Shearer, and C. Chougnet. 2007. Regulatory T-cell markers, indoleamine 2,3-dioxygenase, and virus levels in spleen and gut during progressive simian immunodeficiency virus infection. J. Virol. 81: 11593-11603.
58. Hryniewicz, A., A. Boasso, Y. Edghill-Smith, M. Vaccari, D. Fuchs, D. Venzon, J. Nacsa, M. R. Betts, W. P. Tsai, J. M. Heraud, et al. 2006. CTLA-4 blockade decreases TGF-β, indoleamine 2,3- dioxygenase, and viral RNA expression in tissues of SIVmac251-infected macaques. Blood 108: 3834-3842.
59. Cecchinato, V., E. Tryniszewska, Z. M. Ma, M. Vaccari, A. Boasso, W. P. Tsai, C. Petrovas, D. Fuchs, J. M. Heraud, D. Venzon, et al. 2008. Immune activation driven by CTLA-4 blockade augments viral replication at mucosal sites in simian immunodeficiency virus infection. J. Immunol. 180: 5439-5447.
60. Riley, J. L., and C. H. June. 2007. The road to recovery: translating PD-1 biology into clinical benefit. Trends Immunol. 28: 48-50.
61. Mestas, J., and C. C. Hughes. 2004. Of mice and not men: differences between mouse and human immunology. J. Immunol. 172: 2731-2738.
62. Walker, B. D., and D. R. Burton. 2008. Toward an AIDS vaccine. Science 320: 760-764.
63. Berger, R., R. Rotem-Yehudar, G. Slama, S. Landes, A. Kneller, M. Leiba, M. Koren-Michowitz, A. Shimoni, and A. Nagler. 2008. Phase I safety and pharmacokinetic study of CT-011, a humanized antibody interacting with PD-1, in patients with advanced hematologic malignancies. Clin. Cancer Res. 14: 3044-3051.
64. Finnefrock, A. C., A. Tang, F. Li, D. C. Freed, M. Feng, K. S. Cox, K. J. Sykes, J. P. Guare, M. D. Miller, D. B. Olsen, et al. 2009. PD-1 blockade in rhesus macaques: impact on chronic infection and prophylactic vaccination. J. Immunol. 182: 980-987.
65. Brooks, D. G., A. M. Lee, H. Elsaesser, D. B. McGavern, and M. B. Oldstone. 2008. IL-10 blockade facilitates DNA vaccine-induced T cell responses and enhances clearance of persistent virus infection. J. Exp. Med. 205: 533-541.
66. Brooks, D. G., S. J. Ha, H. Elsaesser, A. H. Sharpe, G. J. Freeman, and M. B. Oldstone. 2008. IL-10 and PD-L1 operate through distinct pathways to suppress T-cell activity during persistent viral infection. Proc. Natl. Acad. Sci. USA 105: 20428-20433.
67. Silvestri, G., and M. B. Feinberg. 2003. Turnover of lymphocytes and conceptual paradigms in HIV infection. J. Clin. Invest. 112: 821-824.
68. Iwai, Y., S. Terawaki, M. Ikegawa, T. Okazaki, and T. Honjo. 2003. PD-1 inhibits antiviral immunity at the effector phase in the liver. J. Exp. Med. 198: 39-50.
69. Daniel, M. D., F. Kirchhoff, S. C. Czajak, P. K. Sehgal, and R. C. Desrosiers. 1992. Protective effects of a live attenuated SIV vaccine with a deletion in the nef gene. Science 258: 1938-1941.
70. Barouch, D. H. 2008. Challenges in the development of an HIV-1 vaccine. Nature 455: 613-619.