PD-1 expression and IL-2 loss of cytomegalovirus- specific t cells correlates with viremia and reversible functional anergy

American Journal of Transplantation

Volumn 8, Issue 7, 2008, Pages 1486-1497

  Sester, U ^a   Presser, D ^a   Dirks, J ^a   Gartner B C ^a   Kohler H ^a   Sester, M ^a  

^a SAARLAND UNIVERSITY   (Germany)

Author keywords

CD4+ T cells; Cellular immunity; Clinical virology; Cytomegalovirus (CMV); Cytomegalovirus infection; Effector T cells; Flow cytometry; Immune monitoring; Infectious complications; Intracellular cytokines; PD 1; Renal transplantation; T cell reactivity

Indexed keywords

GAMMA INTERFERON; IMMUNOSUPPRESSIVE AGENT; INTERLEUKIN 2; METHYLPREDNISOLONE; MYCOPHENOLIC ACID 2 MORPHOLINOETHYL ESTER; PROTEIN PD1; TUMOR PROTEIN; VALGANCICLOVIR;

ADULT; AGED; ARTICLE; CD4+ T LYMPHOCYTE; CD8+ T LYMPHOCYTE; CELL PROLIFERATION; CLINICAL ARTICLE; CLONAL ANERGY; CONTROLLED STUDY; FEMALE; HUMAN; HUMAN CELL; IMMUNOCOMPETENCE; INCUBATION TIME; KIDNEY TRANSPLANTATION; MALE; PRIORITY JOURNAL; PROPHYLAXIS; PROTEIN EXPRESSION; RENAL REPLACEMENT THERAPY; SIGNAL TRANSDUCTION; VIREMIA; VIRUS LOAD;

ADULT; AGED; ANTIGENS, CD; APOPTOSIS REGULATORY PROTEINS; CASE-CONTROL STUDIES; CD4-POSITIVE T-LYMPHOCYTES; CLONAL ANERGY; CYTOMEGALOVIRUS; CYTOMEGALOVIRUS INFECTIONS; FEMALE; GENE EXPRESSION; HUMANS; INTERLEUKIN-2; KIDNEY TRANSPLANTATION; MALE; MIDDLE AGED; VIRAL LOAD; VIREMIA; VIRUS REPLICATION;

EID: 47249101105     PISSN: 16006135     EISSN: 16006143     Source Type: Journal    
DOI: 10.1111/j.1600-6143.2008.02279.x     Document Type: Article

References (35)

1. Freeman GJ, Wherry EJ, Ahmed R, Sharpe AH. Reinvigorating exhausted HIV-specific T cells via PD-1-PD-1 ligand blockade. J Exp Med 2006 203: 2223 2227.
2. Pantaleo G, Harari A. Functional signatures in antiviral T-cell immunity for monitoring virus-associated diseases. Nat Rev Immunol 2006 6: 417 423.
3. Riley JL, June CH. The CD28 family: A T-cell rheostat for therapeutic control of T-cell activation. Blood 2005 105: 13 21.
4. Okazaki T, Honjo T. Rejuvenating exhausted T cells during chronic viral infection. Cell 2006 124: 459 461.
5. Okazaki T, Honjo T. The PD-1-PD-L pathway in immunological tolerance. Trends Immunol 2006 27: 195 201.
6. Riley JL, June CH. The road to recovery: Translating PD-1 biology into clinical benefit. Trends Immunol 2007 28: 48 50.
7. Barber DL, Wherry EJ, Masopust D et al. Restoring function in exhausted CD8 T cells during chronic viral infection. Nature 2006 439: 682 687.
8. Klenerman P, Hill A. T cells and viral persistence: Lessons from diverse infections. Nat Immunol 2005 6: 873 879.
9. Bowen DG, Walker CM. Adaptive immune responses in acute and chronic hepatitis C virus infection. Nature 2005 436: 946 952.
10. Rehermann B, Nascimbeni M. Immunology of hepatitis B virus and hepatitis C virus infection. Nat Rev Immunol 2005 5: 215 229.
11. Wieland SF, Chisari FV. Stealth and cunning: Hepatitis B and hepatitis C viruses. J Virol 2005 79: 9369 9380.
12. Day CL, Kaufmann DE, Kiepiela P et al. PD-1 expression on HIV-specific T cells is associated with T-cell exhaustion and disease progression. Nature 2006 443: 350 354.
13. Trautmann L, Janbazian L, Chomont N et al. Upregulation of PD-1 expression on HIV-specific CD8(+) T cells leads to reversible immune dysfunction. Nat Med 2006 12: 1198 1202.
14. Petrovas C, Casazza JP, Brenchley JM et al. PD-1 is a regulator of virus-specific CD8+ T cell survival in HIV infection. J Exp Med 2006 203: 2281 2292.
15. Urbani S, Amadei B, Tola D et al. PD-1 expression in acute hepatitis C virus (HCV) infection is associated with HCV-specific CD8 exhaustion. J Virol 2006 80: 11398 11403.
16. Radziewicz H, Ibegbu CC, Fernandez ML et al. Liver-infiltrating lymphocytes in chronic human hepatitis C virus infection display an exhausted phenotype with high levels of PD-1 and low levels of CD127 expression. J Virol 2007 81: 2545 2553.
17. Penna A, Pilli M, Zerbini A et al. Dysfunction and functional restoration of HCV-specific CD8 responses in chronic hepatitis C virus infection. Hepatology 2007 45: 588 601.
18. Gandhi MK, Khanna R. Human cytomegalovirus: Clinical aspects, immune regulation, and emerging treatments. Lancet Infect Dis 2004 4: 725 738.
19. Fishman JA, Rubin RH. Infection in organ-transplant recipients. N Engl J Med 1998 338: 1741 1751.
20. Soderberg-Naucler C. Human cytomegalovirus persists in its host and attacks and avoids elimination by the immune system. Crit Rev Immunol 2006 26: 231 264.
21. Sester M, Sester U, Gärtner B et al. Levels of virus-specific CD4 T cells correlate with cytomegalovirus control and predict virus-induced disease after renal transplantation. Transplantation 2001 71: 1287 1294.
22. Sester U, Gärtner BC, Wilkens H et al. Differences in CMV-specific T-cell levels and long-term susceptibility to CMV infection after kidney, heart and lung transplantation. Am J Transplant 2005 5: 1483 1489.
23. Sester M, Sester U, Gärtner B et al. Sustained high frequencies of specific CD4 T cells restricted to a single persistent virus. J Virol 2002 76: 3748 3755.
24. Bunde T, Kirchner A, Hoffmeister B et al. Protection from cytomegalovirus after transplantation is correlated with immediate early 1-specific CD8 T cells. J Exp Med 2005 201: 1031 1036.
25. Iyasere C, Tilton JC, Johnson AJ et al. Diminished proliferation of human immunodeficiency virus-specific CD4+ T cells is associated with diminished interleukin-2 (IL-2) production and is recovered by exogenous IL-2. J Virol 2003 77: 10900 10909.
26. Brooks DG, Teyton L, Oldstone MB, McGavern DB. Intrinsic functional dysregulation of CD4 T cells occurs rapidly following persistent viral infection. J Virol 2005 79: 10514 10527.
27. Wherry EJ, Ahmed R. Memory CD8 T-cell differentiation during viral infection. J Virol 2004 78: 5535 5545.
28. Zajac AJ, Blattman JN, Murali-Krishna K et al. Viral immune evasion due to persistence of activated T cells without effector function. J Exp Med 1998 188: 2205 2213.
29. Wherry EJ, Blattman JN, 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 2003 77: 4911 4927.
30. Harari A, Dutoit V, Cellerai C, Bart PA, Du Pasquier RA, Pantaleo G. Functional signatures of protective antiviral T-cell immunity in human virus infections. Immunol Rev 2006 211: 236 254.
31. Harari A, Vallelian F, Meylan PR, Pantaleo G. Functional heterogeneity of memory CD4 T cell responses in different conditions of antigen exposure and persistence. J Immunol 2005 174: 1037 1045.
32. Sagedal S, Hartmann A, Nordal KP et al. Impact of early cytomegalovirus infection and disease on long-term recipient and kidney graft survival. Kidney Int 2004 66: 329 337.
33. Schnitzler MA, Lowell JA, Hmiel SP et al. Cytomegalovirus disease after prophylaxis with oral ganciclovir in renal transplantation: The importance of HLA-DR matching. J Am Soc Nephrol 2003 14: 780 785.
34. Opelz G, Dohler B, Ruhenstroth A. Cytomegalovirus prophylaxis and graft outcome in solid organ transplantation: A collaborative transplant study report. Am J Transplant 2004 4: 928 936.
35. Hammer MH, Meyer S, Brestrich G et al. HLA type-independent generation of antigen-specific T cells for adoptive immunotherapy. Eur J Immunol 2005 35: 2250 2258.