Elevated expression of CD160 and 2B4 defines a cytolytic HIV-specific CD8+ T-cell population in elite controllers

Journal of Infectious Diseases

Volumn 212, Issue 9, 2015, Pages 1376-1386

  Pombo, Carolina ^a   Wherry, E John ^a   Gostick, Emma ^c   Price, David A ^b,c   Betts, Michael R ^a,d  

^a UNIVERSITY OF PENNSYLVANIA   (United States)

^b NATIONAL INSTITUTES OF HEALTH   (United States)

^c CARDIFF UNIVERSITY SCHOOL OF MEDICINE   (United Kingdom)

^d UNIVERSITY OF PENNSYLVANIA   (United States)

Author keywords

2B4; CD160; CD8+ T cells; elite controllers; HIV; PD 1; T cell exhaustion

Indexed keywords

CD160 PROTEIN; CELL PROTEIN; CYTOCHROME P450 2B4; EPITOPE; LAG 3 PROTEIN; PROGRAMMED DEATH 1 RECEPTOR; UNCLASSIFIED DRUG; CD160 PROTEIN, HUMAN; CD223 ANTIGEN; CD244 PROTEIN, HUMAN; GENETIC MARKER; GLYCOSYLPHOSPHATIDYLINOSITOL ANCHORED PROTEIN; IMMUNOGLOBULIN RECEPTOR; LEUKOCYTE ANTIGEN; PDCD1 PROTEIN, HUMAN; PERFORIN; SIGNALING LYMPHOCYTIC ACTIVATION MOLECULE; VIRUS RNA;

ARTICLE; CD8+ T LYMPHOCYTE; CELL EXHAUSTION; CELLULAR PARAMETERS; COHORT ANALYSIS; CONTROLLED STUDY; CORRELATIONAL STUDY; CYTOLYSIS; DISEASE COURSE; ELITE CONTROLLER; HUMAN; HUMAN CELL; HUMAN IMMUNODEFICIENCY VIRUS INFECTION; INFECTION; INFECTION CONTROL; LYMPHOCYTE SUBPOPULATION; MEMORY CELL; PRIORITY JOURNAL; PROTEIN EXPRESSION; BLOOD; CHRONIC DISEASE; GENETIC MARKER; GENETICS; HUMAN IMMUNODEFICIENCY VIRUS 1; IMMUNOLOGY; METABOLISM; MONONUCLEAR CELL; VIROLOGY;

ANTIGENS, CD; CD8-POSITIVE T-LYMPHOCYTES; CHRONIC DISEASE; GENETIC MARKERS; GPI-LINKED PROTEINS; HIV INFECTIONS; HIV-1; HUMANS; LEUKOCYTES, MONONUCLEAR; PERFORIN; PROGRAMMED CELL DEATH 1 RECEPTOR; RECEPTORS, IMMUNOLOGIC; RNA, VIRAL; SIGNALING LYMPHOCYTIC ACTIVATION MOLECULE FAMILY;

EID: 84946103709     PISSN: 00221899     EISSN: 15376613     Source Type: Journal    
DOI: 10.1093/infdis/jiv226     Document Type: Article

References (50)

1. Gulzar N, Copeland K. CD8+ T-cells: function and response to HIV infection. Curr HIV Res 2004; 2: 23-37
2. El-Far M, Halwani R, Said E, et al. T-cell exhaustion in HIV infection. Curr HIV/AIDS Rep 2008; 5: 13-9
3. Makedonas G, Hutnick N, Haney D, et al. Perforin and IL-2 upregulation define qualitative differences among highly functional virus-specific human CD8 T cells. PLoS Pathog 2010; 6: e1000798
4. Hersperger AR, Pereyra F, Nason M, et al. Perforin expression directly ex vivo by HIV-specific CD8 T-cells is a correlate of HIV elite control. PLoS Pathog 2010; 6: e1000917
5. Betts MR, Nason MC, West SM, et al. HIV nonprogressors preferentially maintain highly functional HIV-specific CD8+ T cells. Blood 2006; 107: 4781-9
6. Migueles SA, Osborne CM, Royce C, et al. Lytic granule loading of CD8+ T cells is required for HIV-infected cell elimination associated with immune control. Immunity 2008; 29: 1009-21
7. Gea-Banacloche JC, Migueles SA, Martino L, et al. Maintenance of large numbers of virus-specific CD8+ T cells in HIV-infected progressors and long-term nonprogressors. The J Immunol 2000; 165: 1082-92
8. Sáez-Cirión A, Lacabaratz C, Lambotte O, et al. HIV controllers exhibit potent CD8 T cell capacity to suppress HIV infection ex vivo and peculiar cytotoxic T lymphocyte activation phenotype. Proc Natl Acad Sci USA 2007; 104: 6776-81
9. Schellens IMM, Borghans JAM, Jansen CA, et al. Abundance of early functional HIV-specific CD8+ T cells does not predict AIDS-free survival time. PLoS One 2008; 3: e2745
10. Betts MR, Ambrozak DR, Douek DC, et al. Analysis of total human immunodeficiency virus (HIV)-specific CD4(+) and CD8(+) T-cell responses: relationship to viral load in untreated HIV infection. J Virol 2001; 75: 11983-91
11. Almeida JR, Price DA, Papagno L, et al. Superior control of HIV-1 replication by CD8+ T cells is reflected by their avidity, polyfunctionality, and clonal turnover. J Exp Med 2007; 204: 2473-85
12. Schmitz JE, Kuroda MJ, Santra S, et al. Control of viremia in simian immunodeficiency virus infection by CD8+ lymphocytes. Science 1999; 283: 857-60
13. Jin X, Bauer DE, Tuttleton SE, et al. Dramatic rise in plasma viremia after CD8(+) T cell depletion in simian immunodeficiency virus-infected macaques. J Exp Med 1999; 189: 991-8
14. Peretz Y, He Z, Shi Y, et al. CD160 and PD-1 co-expression on HIVspecific CD8 T cells defines a subset with advanced dysfunction. PLoS Pathog 2012; 8: e1002840
15. 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: 1198-202
16. Yamamoto T, Price DA, Casazza JP, et al. Surface expression patterns of negative regulatory molecules identify determinants of virus-specific CD8+ T-cell exhaustion in HIV infection. Blood 2011; 117: 4805-15
17. Blackburn SD, Shin H, Haining WN, et al. Coregulation of CD8+ T cell exhaustion by multiple inhibitory receptors during chronic viral infection. Nat Immunol 2008; 10: 29-37
18. Bucks CM, Norton JA, Boesteanu AC, Mueller YM, Katsikis PD. Chronic antigen stimulation alone is sufficient to drive CD8+ T cell exhaustion. J Immunol 2009; 182: 6697-708
19. Jackson SR, Berrien-Elliott MM, Meyer JM, Wherry EJ, Teague RM. CD8+ T cell exhaustion during persistent viral infection is regulated independently of the virus-specific T cell receptor. Immunol Invest 2013; 42: 204-20
20. Utzschneider DT, Legat A, Fuertes Marraco SA, et al. T cells maintain an exhausted phenotype after antigen withdrawal and population reexpansion. Nat Immunol 2013; 14: 603-10
21. Petrovas C, Price DA, Mattapallil J, 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: 928-36
22. Velu V, Kannanganat S, Ibegbu C, et al. 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 2007; 81: 5819-28
23. Kroy DC, Ciuffreda D, Cooperrider JH, et al. Liver environment and HCV replication affect human T-cell phenotype and expression of inhibitory receptors. Gastroenterology 2014; 146: 550-61
24. Bengsch B, Seigel B, Ruhl M, et al. Coexpression of PD-1, 2B4, CD160 and KLRG1 on exhausted HCV-specific CD8+ T cells is linked to antigen recognition and T cell differentiation. PLoS Pathog 2010; 6: e1000947
25. Riches JC, Davies JK, McClanahan F, et al. T cells from CLL patients exhibit features of T-cell exhaustion but retain capacity for cytokine production. Blood 2013; 121: 1612-21
26. Fourcade J, Sun Z, Pagliano O, et al. CD8(+) T cells specific for tumor antigens can be rendered dysfunctional by the tumor microenvironment through upregulation of the inhibitory receptors BTLA and PD-1. Cancer Res 2012; 72: 887-96
27. Wherry EJ, Ha S-J, Kaech SM, et al. Molecular signature of CD8+T cell exhaustion during chronic viral infection. Immunity 2007; 27: 670-84
28. Aldy KN, Horton NC, Mathew PA, Mathew SO. 2B4+ CD8+ T cells play an inhibitory role against constrained HIV epitopes. Biochem Biophys Res Commun 2011; 405: 503-7
29. 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: 350-4
30. Petrovas C, Casazza JP, Brenchley JM, et al. PD-1 is a regulator of virusspecific CD8+ T cell survival in HIV infection. J Exp Med 2006; 203: 2281-92
31. Rey J, Giustiniani J, Mallet F, et al. The co-expression of 2B4 (CD244) and CD160 delineates a subpopulation of human CD8+ T cells with a potent CD160-mediated cytolytic effector function. Eur J Immunol 2006; 36: 2359-66
32. Viganò S, Banga R, Bellanger F, et al. CD160-Associated CD8 T-Cell Functional Impairment Is Independent of PD-1 Expression. PLoS Pathog 2014; 10: e1004380
33. Cai G, Anumanthan A, Brown JA, et al. CD160 inhibits activation of human CD4+ T cells through interaction with herpesvirus entry mediator. Nat Immunol 2008; 9: 176-85
34. Chattopadhyay PK, Price DA, Harper TF, et al. Quantum dot semiconductor nanocrystals for immunophenotyping by polychromatic flow cytometry. Nat Med 2006; 12: 972-7
35. Price DA, Brenchley JM, Ruff LE, et al. Avidity for antigen shapes clonal dominance in CD8+ T cell populations specific for persistent DNA viruses. J Exp Med 2005; 202: 1349-61
36. Perfetto SP, Ambrozak D, Nguyen R, Chattopadhyay PK, Roederer M. Quality assurance for polychromatic flow cytometry using a suite of calibration beads. Nat Protoc 2012; 7: 2067-79
37. Zhang JY, Zhang Z, Wang X, et al. PD-1 up-regulation is correlated with HIV-specific memory CD8+ T-cell exhaustion in typical progressors but not in long-term nonprogressors. Blood 2007; 109: 4671-8
38. Nikolova MH, Muhtarova MN, Taskov HB, et al. The CD160+CD8high cytotoxic T cell subset correlates with response to HAART in HIV-1+ patients. Cell Immunol 2005; 237: 96-105
39. Šedý JR, Bjordahl RL, Bekiaris V, et al. CD160 activation by herpesvirus entry mediator augments inflammatory cytokine production and cytolytic function by NK cells. J Immunol 2013; 191: 828-36
40. Nikolova M, Cardine AM, Boumsell L. BY55/CD160 acts as a co-receptor in TCR signal transduction of a human circulating cytotoxic effector T lymphocyte subset lacking CD28 expression. Int Immunol 2002; 14: 445-51
41. Meinke S, Watzl C. NK cell cytotoxicity mediated by 2B4 and NTB-A is dependent on SAP acting downstream of receptor phosphorylation. Front Immunol 2013; 4: 3
42. Schlaphoff V, Lunemann S, Suneetha PV, et al. Dual function of the NK cell receptor 2B4 (CD244) in the regulation of HCV-specific CD8+T cells. PLoS Pathog 2011; 7: e1002045
43. Sinha SK, Gao N, Guo Y, Yuan D. Mechanism of induction of NK activation by 2B4 (CD244) via its cognate ligand. J Immunol 2010; 185: 5205-10
44. Bailey JR, Brennan TP, O Connell KA, Siliciano RF, Blankson JN. Evidence of CD8+ T-cell-mediated selective pressure on human immunodeficiency virus type 1 nef in HLA-B∗57+ elite suppressors. J Virol 2008; 83: 88-97
45. Barber DL, Wherry EJ, Masopust D, et al. Restoring function in exhausted CD8 T cells during chronic viral infection. Nature 2005; 439: 682-7
46. Doering TA, Crawford A, Angelosanto JM, et al. Network analysis reveals centrally connected genes and pathways involved in CD8+ T cell exhaustion versus memory. Immunity 2012; 37: 1130-44
47. El-Far M, Pellerin C, Pilote L, et al. CD160 isoforms and regulation of CD4 and CD8 T-cell responses. J Transl Med 2014; 12: 217
48. Harvey RD. Immunologic and clinical effects of targeting PD-1 in lung cancer. Clin Pharmacol Ther 2014; 96: 214-23
49. Baitsch L, Legat A, Barba L, et al. Extended co-expression of inhibitory receptors by human CD8 T-Cells depending on differentiation, antigen-specificity and anatomical localization. PLoS One 2012; 7: e30852
50. Legat A, Speiser DE, Pircher H, Zehn D, Fuertes Marraco SA. Inhibitory receptor expression depends more dominantly on differentiation and activation than exhaustion of human CD8 T cells. Front Immunol 2013; 4: 455