Exhaustion of Activated CD8 T Cells Predicts Disease Progression in Primary HIV-1 Infection

PLoS Pathogens

Volumn 12, Issue 7, 2016, Pages

  Hoffmann, Matthias ^a,b   Pantazis, Nikos ^c,d   Martin, Genevieve E ^a   Hickling, Stephen ^a   Hurst, Jacob ^a,e   Meyerowitz, Jodi ^a   Willberg, Christian B ^a,f   Robinson, Nicola ^a,f   Brown, Helen ^a,f   Fisher, Martin ^g   Kinloch, Sabine ^h   Babiker, Abdel ^d   Weber, Jonathan ⁱ   Nwokolo, Nneka ^j   Fox, Julie ^k   Fidler, Sarah ⁱ   Phillips, Rodney ^a,e,f   Frater, John ^a,e,f  

^a UNIVERSITY OF OXFORD   (United Kingdom)

^b CANTONAL HOSPITAL ST GALLEN   (Switzerland)

^c UNIVERSITY OF ATHENS MEDICAL SCHOOL   (Greece)

^d MRC CLINICAL TRIALS UNIT   (United Kingdom)

^e UNIVERSITY OF OXFORD   (United Kingdom)

^f NIHR OXFORD BIOMEDICAL RESEARCH CENTRE   (United Kingdom)

^g UK   (United Kingdom)

^h UNIVERSITY COLLEGE LONDON   (United Kingdom)

ⁱ IMPERIAL COLLEGE LONDON   (United Kingdom)

^j CHELSEA AND WESTMINSTER HOSPITAL   (United Kingdom)

^k GUY'S AND ST THOMAS' NHS FOUNDATION TRUST   (United Kingdom)

more..

Author keywords

[No Author keywords available]

Indexed keywords

PEPTIDES AND PROTEINS; PROGRAMMED DEATH 1 RECEPTOR; T CELL IMMUNOGLOBULIN AND MUCIN DOMAIN 3; UNCLASSIFIED DRUG; ANTIRETROVIRUS AGENT; BIOLOGICAL MARKER; CD223 ANTIGEN; HAVCR2 PROTEIN, HUMAN; HEPATITIS A VIRUS CELLULAR RECEPTOR 2; LEUKOCYTE ANTIGEN; PDCD1 PROTEIN, HUMAN;

ADULT; ARTICLE; CD4 LYMPHOCYTE COUNT; CD8+ T LYMPHOCYTE; CONTROLLED STUDY; DISEASE COURSE; DISEASE MARKER; FEMALE; FLOW CYTOMETRY; GENE; HIGHLY ACTIVE ANTIRETROVIRAL THERAPY; HUMAN; HUMAN IMMUNODEFICIENCY VIRUS 1 INFECTION; LYMPHOCYTE ACTIVATION GENE 3; MAJOR CLINICAL STUDY; MALE; VIRUS EXPRESSION; VIRUS LOAD; BIOSYNTHESIS; HIV INFECTIONS; HUMAN IMMUNODEFICIENCY VIRUS 1; IMMUNOLOGY; LYMPHOCYTE ACTIVATION; RANDOMIZED CONTROLLED TRIAL;

ADULT; ANTI-RETROVIRAL AGENTS; ANTIGENS, CD; BIOMARKERS; CD8-POSITIVE T-LYMPHOCYTES; DISEASE PROGRESSION; FEMALE; FLOW CYTOMETRY; HEPATITIS A VIRUS CELLULAR RECEPTOR 2; HIV INFECTIONS; HIV-1; HUMANS; LYMPHOCYTE ACTIVATION; MALE; PROGRAMMED CELL DEATH 1 RECEPTOR;

EID: 84982896889     PISSN: 15537366     EISSN: 15537374     Source Type: Journal    
DOI: 10.1371/journal.ppat.1005661     Document Type: Article

References (40)

1. Feeney ME, Tang Y, Roosevelt KA, Leslie AJ, McIntosh K, Karthas N, et al. Immune escape precedes breakthrough human immunodeficiency virus type 1 viremia and broadening of the cytotoxic T-lymphocyte response in an HLA-B27-positive long-term-nonprogressing child. J Virol. 2004;78: 8927–8930. 15280502
2. Frater AJ, Brown H, Oxenius A, Gunthard HF, Hirschel B, Robinson N, et al. Effective T-cell responses select human immunodeficiency virus mutants and slow disease progression. J Virol. 2007;81: 6742–6751. 17409157
3. Goulder P, Price D, Nowak M, Rowland-Jones S, Phillips R, McMichael A, Co-evolution of human immunodeficiency virus and cytotoxic T-lymphocyte responses. Immunol Rev. 1997;159: 17–29. 9416500
4. Kiepiela P, Leslie AJ, Honeyborne I, Ramduth D, Thobakgale C, Chetty S, et al. Dominant influence of HLA-B In mediating the potential co-evolution of HIV and HLA. Nature. 2004;432: 769–774. 15592417
5. Leslie AJ, Pfafferott KJ, Chetty P, Draenert R, Addo MM, Feeney M, et al. HIV evolution: CTL escape mutation and reversion after transmission. Nat Med. 2004;10: 282–289. 14770175
6. Grakoui A, Bromley SK, Sumen C, Davis MM, Shaw AS, Allen PM, et al. The immunological synapse: a molecular machine controlling T cell activation. Science. 1999;285: 221–227. 10398592
7. Kalergis AM, Boucheron N, Doucey MA, Palmieri E, Goyarts EC, Vegh Z, et al. Efficient T cell activation requires an optimal dwell-time of interaction between the TCR and the pMHC complex. Nat Immunol. 2001;2: 229–234. 11224522
8. Miceli MC, Parnes JR, Role of CD4 and CD8 in T cell activation and differentiation. Adv Immunol. 1993;53: 59–122. 8512039
9. Brunet JF, Denizot F, Luciani MF, Roux-Dosseto M, Suzan M, Mattei MG, et al. A new member of the immunoglobulin superfamily—CTLA-4. Nature. 1987;328: 267–270. 3496540
10. Lenschow DJ, Bluestone JA, T cell co-stimulation and in vivo tolerance. Curr Opin Immunol. 1993;5: 747–752. 7694594
11. Chen L, Flies DB, Molecular mechanisms of T cell co-stimulation and co-inhibition. Nat Rev Immunol. 2013;13: 227–242. doi: 10.1038/nri340523470321
12. Day CL, Kaufmann DE, Kiepiela P, Brown JA, Moodley ES, Reddy S, et al. PD-1 expression on HIV-specific T cells is associated with T-cell exhaustion and disease progression. Nature. 2006;443: 350–354. 16921384
13. Gruener NH, Lechner F, Jung MC, Diepolder H, Gerlach T, Lauer G, et al. Sustained dysfunction of antiviral CD8+ T lymphocytes after infection with hepatitis C virus. J Virol. 2001;75: 5550–5558. 11356962
14. Lechner F, Sullivan J, Spiegel H, Nixon DF, Ferrari B, Davis A, et al. Why do cytotoxic T lymphocytes fail to eliminate hepatitis C virus? Lessons from studies using major histocompatibility complex class I peptide tetramers. Philos Trans R Soc Lond, B, Biol Sci. 2000;355: 1085–1092. 11186310
15. Wherry EJ, Ha S-J, Kaech SM, Haining WN, Sarkar S, Kalia V, et al. Molecular signature of CD8+ T cell exhaustion during chronic viral infection. Immunity. 2007;27: 670–684. 17950003
16. Zajac AJ, Blattman JN, Murali-Krishna K, Sourdive DJ, Suresh M, Altman JD, et al. Viral immune evasion due to persistence of activated T cells without effector function. J Exp Med. 1998;188: 2205–2213. 9858507
17. Blackburn SD, Shin H, Haining WN, Zou T, Workman CJ, Polley A, et al. Coregulation of CD8+ T cell exhaustion by multiple inhibitory receptors during chronic viral infection. Nature Immunology. 2008;10: 29–37. doi: 10.1038/ni.167919043418
18. Jones RB, Ndhlovu LC, Barbour JD, Sheth PM, Jha AR, Long BR, et al. Tim-3 expression defines a novel population of dysfunctional T cells with highly elevated frequencies in progressive HIV-1 infection. Journal of Experimental Medicine. 2008;205: 2763–2779. doi: 10.1084/jem.2008139819001139
19. Petrovas C, Price DA, Mattapallil J, Ambrozak DR, Geldmacher C, Cecchinato V, et al. SIV-specific CD8+ T cells express high levels of PD1 and cytokines but have impaired proliferative capacity in acute and chronic SIVmac251 infection. Blood. 2007;110: 928–936. 17440051
20. Trautmann L, Janbazian L, Chomont N, Said EA, Gimmig S, Bessette B, et al. Upregulation of PD-1 expression on HIV-specific CD8+ T cells leads to reversible immune dysfunction. Nat Med. 2006;12: 1198–1202. 16917489
21. Hurst J, Hoffmann M, Pace M, Williams JP, Thornhill J, Hamlyn E, et al. Immunological biomarkers predict HIV-1 viral rebound after treatment interruption. Nat Commun. 2015;6: 8495. doi: 10.1038/ncomms949526449164
22. Chomont N, Far El M, Ancuta P, Trautmann L, Procopio FA, Yassine-Diab B, et al. HIV reservoir size and persistence are driven by T cell survival and homeostatic proliferation. Nat Med. 2009;15: 893–900. doi: 10.1038/nm.197219543283
23. SPARTAC Trial InvestigatorsFidler S, Porter K, Ewings F, Frater J, Ramjee G, et al. Short-course antiretroviral therapy in primary HIV infection. N Engl J Med. 2013 ed. 2013;368: 207–217. doi: 10.1056/NEJMoa111003923323897
24. Buggert M, Tauriainen J, Yamamoto T, Frederiksen J, Ivarsson MA, Michaëlsson J, et al. T-bet and Eomes are differentially linked to the exhausted phenotype of CD8+ T cells in HIV infection. PLoS Pathog. 2014;10: e1004251. doi: 10.1371/journal.ppat.100425125032686
25. Gupta PK, Godec J, Wolski D, Adland E, Yates K, Pauken KE, et al. CD39 Expression Identifies Terminally Exhausted CD8+ T Cells. PLoS Pathog. 2015;11: e1005177. doi: 10.1371/journal.ppat.100517726485519
26. Roederer M, Quaye L, Mangino M, Beddall MH, Mahnke Y, Chattopadhyay P, et al. The genetic architecture of the human immune system: a bioresource for autoimmunity and disease pathogenesis. Cell. 2015;161: 387–403. doi: 10.1016/j.cell.2015.02.04625772697
27. Wei F, Zhong S, Ma Z, Kong H, Medvec A, Ahmed R, et al. Strength of PD-1 signaling differentially affects T-cell effector functions. Proceedings of the National Academy of Sciences of the United States of America. 2013;110: E2480–E2489. doi: 10.1073/pnas.130539411023610399
28. Sakuishi K, Jayaraman P, Behar SM, Anderson AC, Kuchroo VK, Emerging Tim-3 functions in antimicrobial and tumor immunity. Trends in Immunology. 2011;32: 345–349. doi: 10.1016/j.it.2011.05.00321697013
29. Topalian SL, Hodi FS, Brahmer JR, Gettinger SN, Smith DC, McDermott DF, et al. Safety, Activity, and Immune Correlates of Anti–PD-1 Antibody in Cancer. N Engl J Med. 2012;366: 2443–2454. doi: 10.1056/NEJMoa120069022658127
30. Brahmer JR, Tykodi SS, Chow LQM, Hwu W-J, Topalian SL, Hwu P, et al. Safety and Activity of Anti–PD-L1 Antibody in Patients with Advanced Cancer. N Engl J Med. 2012;366: 2455–2465. doi: 10.1056/NEJMoa120069422658128
31. Giorgi JV, Hultin LE, McKeating JA, Johnson TD, Owens B, Jacobson L. P., et al. Shorter survival in advanced human immunodeficiency virus type 1 infection is more closely associated with T lymphocyte activation than with plasma virus burden or virus chemokine coreceptor usage. J Infect Dis. 1999;179: 859–870. 10068581
32. Price P, Keane N, Gray L, Lee S, Gorry PR, French MA, Brief Report: CXCR4 or CCR5 tropism of human immunodeficiency virus type 1 isolates does not determine the immunological milieu in patients responding to antiretroviral therapy. Viral immunology. Mary Ann Liebert, Inc. 2 Madison Avenue Larchmont, NY 10538 USA; 2006;19: 734–740.
33. Lim AY-F, Price P, Beilharz MW, French MA, Cell surface markers of regulatory T cells are not associated with increased forkhead box p3 expression in blood CD4+ T cells from HIV-infected patients responding to antiretroviral therapy. Immunology and Cell Biology. 2006;84: 530–536. 16956389
34. Juno JA, Stalker AT, Waruk JL, Oyugi J, Kimani M, Plummer FA, et al. Elevated expression of LAG-3, but not PD-1, is associated with impaired iNKT cytokine production during chronic HIV-1 infection and treatment. Retrovirology. 2015;12: 17. doi: 10.1186/s12977-015-0142-z25810006
35. Ferris RL, Lu B, Kane LP, Too Much of a Good Thing? Tim-3 and TCR Signaling in T Cell Exhaustion. The Journal of Immunology. 2014;193: 1525–1530. doi: 10.4049/jimmunol.140055725086175
36. Jin H-T, Anderson AC, Tan WG, West EE, Ha S-J, Araki K, et al. Cooperation of Tim-3 and PD-1 in CD8 T-cell exhaustion during chronic viral infection. Proceedings of the National Academy of Sciences. 2010;107: 14733–14738.
37. Youngblood B, Noto A, Porichis F, Akondy RS, Ndhlovu ZM, Austin JW, et al. Cutting edge: Prolonged exposure to HIV reinforces a poised epigenetic program for PD-1 expression in virus-specific CD8 T cells. J Immunol. 2013;191: 540–544. doi: 10.4049/jimmunol.120316123772031
38. Paley MA, Kroy DC, Odorizzi PM, Johnnidis JB, Dolfi DV, Barnett BE, et al. Progenitor and terminal subsets of CD8+ T cells cooperate to contain chronic viral infection. Science. 2012;338: 1220–1225. doi: 10.1126/science.122962023197535
39. Roederer M, Spectral compensation for flow cytometry: visualization artifacts, limitations, and caveats. Cytometry B Clin Cytom. 2001;45: 194–205.
40. Simes RJ, An improved Bonferroni procedure for multiple tests of significance. Biometrica. 1986;73: 751–754.