The efficiency of the human CD8+ T cell response: How should we quantify it, what determines it, and does it matter?

PLoS Computational Biology

Volumn 8, Issue 2, 2012, Pages

  Elemans, Marjet ^a   Seich al Basatena, Nafisa Katrin ^a   Asquith, Becca ^a  

^a IMPERIAL COLLEGE SCHOOL OF MEDICINE   (United Kingdom)

Author keywords

[No Author keywords available]

Indexed keywords

T-CELLS; VIRUSES;

CLASS I; EPITOPE PREDICTIONS; EXPERIMENTAL APPROACHES; IN-VIVO; T-CELL RESPONSE; THEORETICAL TECHNIQUE; VIRUS-INFECTED CELLS;

EFFICIENCY;

HLA ANTIGEN CLASS 1; KILLER CELL IMMUNOGLOBULIN LIKE RECEPTOR 2DL2; EPITOPE; LIGAND; LYMPHOCYTE ANTIGEN RECEPTOR;

ADAPTIVE IMMUNITY; ALGORITHM; ANTIGEN RECOGNITION; CD8+ T LYMPHOCYTE; CELL KINETICS; HLA SYSTEM; HUMAN; IMMUNOREACTIVITY; INNATE IMMUNITY; MATHEMATICAL COMPUTING; MATHEMATICAL MODEL; MATHEMATICS; NATURAL KILLER CELL; QUANTITATIVE ANALYSIS; REVIEW; T LYMPHOCYTE ACTIVATION; VIRUS CELL INTERACTION; VIRUS IMMUNITY; VIRUS LOAD; VIRUS REPLICATION; VIRUS VIRULENCE; ARTICLE; BIOLOGICAL MODEL; BIOLOGY; CHEMISTRY; CYTOLOGY; METHODOLOGY; PHENOTYPE; THEORETICAL MODEL;

CD8-POSITIVE T-LYMPHOCYTES; COMPUTATIONAL BIOLOGY; EPITOPES; HISTOCOMPATIBILITY ANTIGENS CLASS I; HUMANS; LIGANDS; MODELS, BIOLOGICAL; MODELS, THEORETICAL; PHENOTYPE; RECEPTORS, ANTIGEN, T-CELL;

EID: 84861149866     PISSN: 1553734X     EISSN: 15537358     Source Type: Journal    
DOI: 10.1371/journal.pcbi.1002381     Document Type: Review

References (83)

1. Wick WD, Yang OO, Corey L, Self SG, (2005) How many human immunodeficiency virus type 1-infected target cells can a cytotoxic T-lymphocyte kill? J Virol 79: 13579-13586.
2. Chun TW, Justement JS, Sanford C, Hallahan CW, Planta MA, et al. (2004) Relationship between the frequency of HIV-specific CD8+ T cells and the level of CD38+CD8+ T cells in untreated HIV-infected individuals. Proc Natl Acad Sci U S A 101: 2464-2469.
3. Gea-Banacloche JC, Migueles SA, Martino L, Shupert WL, McNeil AC, et al. (2000) Maintenance of large numbers of virus-specific CD8+ T cells in HIV-infected progressors and long-term nonprogressors. J Immunol 165: 1082-1092.
4. Markowitz M, Louie M, Hurley A, Sun E, Di Mascio M, et al. (2003) A novel antiviral intervention results in more accurate assessment of human immunodeficiency virus type 1 replication dynamics and T-cell decay in vivo. J Virol 77: 5037-5038.
5. Boyd MA, Dixit NM, Siangphoe U, Buss NE, Salgo MP, et al. (2006) Viral decay dynamics in HIV-infected patients receiving ritonavir-boosted saquinavir and efavirenz with or without enfuvirtide: a randomized, controlled trial (HIV-NAT 012). J Infect Dis 194: 1319-1322.
6. Asquith B, Edwards CT, Lipsitch M, McLean AR, (2006) Inefficient cytotoxic T lymphocyte-mediated killing of HIV-1-infected cells in vivo. PLoS Biol 4: e90 doi:10.1371/journal.pbio.0040090.
7. Asquith B, (2008) The evolutionary selective advantage of HIV-1 escape variants and the contribution of escape to the HLA-associated risk of AIDS progression. PLoS ONE 3: e3486 doi:10.1371/journal.pone.0003486.
8. Klenerman P, Phillips RE, Rinaldo CR, Wahl LM, Ogg G, et al. (1996) Cytotoxic T lymphocytes and viral turnover in HIV type 1 infection. Proc Natl Acad Sci U S A 93: 15323-15328.
9. Klatt NR, Shudo E, Ortiz AM, Engram JC, Paiardini M, et al. (2010) CD8+ lymphocytes control viral replication in SIVmac239-infected rhesus macaques without decreasing the lifespan of productively infected cells. PLoS Pathog 6: e1000747 doi:10.1371/journal.ppat.1000747.
10. Wong JK, Strain MC, Porrata R, Reay E, Sankaran-Walters S, et al. (2010) In vivo CD8+ T-cell suppression of siv viremia is not mediated by CTL clearance of productively infected cells. PLoS Pathog 6: e1000748 doi:10.1371/journal.ppat.1000748.
11. Mohri H, Perelson AS, Tung K, Ribeiro RM, Ramratnam B, et al. (2001) Increased turnover of T lymphocytes in HIV-1 infection and its reduction by antiretroviral therapy. J Exp Med 194: 1277-1287.
12. Li Q, Duan L, Estes JD, Ma ZM, Rourke T, et al. (2005) Peak SIV replication in resting memory CD4+ T cells depletes gut lamina propria CD4+ T cells. Nature 434: 1148-1152.
13. Appay V, Nixon DF, Donahoe SM, Gillespie GM, Dong T, et al. (2000) HIV-specific CD8(+) T cells produce antiviral cytokines but are impaired in cytolytic function. J Exp Med 192: 63-75.
14. Bevan MJ, Braciale TJ, (1995) Why can't cytotoxic T cells handle HIV? Proc Natl Acad Sci U S A 92: 5765-5767.
15. Zhang D, Shankar P, Xu Z, Harnisch B, Chen G, et al. (2003) Most antiviral CD8 T cells during chronic viral infection do not express high levels of perforin and are not directly cytotoxic. Blood 101: 226-235.
16. Betts MR, Nason MC, West SM, De Rosa SC, Migueles SA, et al. (2006) HIV nonprogressors preferentially maintain highly functional HIV-specific CD8+ T cells. Blood 107: 4781-4789.
17. Goonetilleke N, Liu MK, Salazar-Gonzalez JF, Ferrari G, Giorgi E, et al. (2009) The first T cell response to transmitted/founder virus contributes to the control of acute viremia in HIV-1 infection. J Exp Med 206: 1253-1272.
18. Ganusov VV, Goonetilleke N, Liu MK, Ferrari G, Shaw GM, et al. (2011) Fitness costs and diversity of CTL response determine the rate of CTL escape during the acute and chronic phases of HIV infection. J Virol 85: 10518-10528.
19. Elemans M, Nafisa-Katrin Seich al Basatena K, Klatt N, Gkekas C, Silvestri G, et al. (2011) Why don't CD8+ T cells reduce the lifespan of SIV-infected cells in vivo? PLoS Comput Biol 7: e1002200 doi:10.1371/journal.pcbi.1002200.
20. Regoes RR, Antia R, Garber DA, Silvestri G, Feinberg MB, et al. (2004) Roles of target cells and virus-specific cellular immunity in primary simian immunodeficiency virus infection. J Virol 78: 4866-4875.
21. Elemans M, Thiebaut R, Kaur A, Asquith B, (2011) Quantification of the relative importance of CTL, B cell, NK cell, and target cell limitation in the control of primary SIV-infection. PLoS Comput Biol 7: e1001103 doi:10.1371/journal.pcbi.1001103.
22. Asquith B, McLean A, (2007) In vivo CD8+ T cell killing of immunodeficiency virus-infected cells in humans and macaques. Proc Natl Acad Sci U S A 104 (15): 6365-6370.
23. Love TM, Thurston SW, Keefer MC, Dewhurst S, Lee HY, (2010) Mathematical modeling of ultradeep sequencing data reveals that acute CD8+ T-lymphocyte responses exert strong selective pressure in simian immunodeficiency virus-infected macaques but still fail to clear founder epitope sequences. J Virol 84: 5802-5814.
24. Fernandez CS, Stratov I, De Rose R, Walsh K, Dale CJ, et al. (2005) Rapid viral escape at an immunodominant simian-human immunodeficiency virus cytotoxic T-lymphocyte epitope exacts a dramatic fitness cost. J Virol 79: 5721-5731.
25. Mandl JN, Regoes RR, Garber DA, Feinberg MB, (2007) Estimating the effectiveness of simian immunodeficiency virus-specific CD8+ T cells from the dynamics of viral immune escape. J Virol 81: 11982-11991.
26. Regoes RR, Barber DL, Ahmed R, Antia R, (2007) Estimation of the rate of killing by cytotoxic T lymphocytes in vivo. Proc Natl Acad Sci U S A 104: 1599-1603.
27. Yates A, Graw F, Barber DL, Ahmed R, Regoes RR, et al. (2007) Revisiting estimates of CTL killing rates in vivo. PLoS ONE 2: e1301 doi:10.1371/journal.pone.0001301.
28. Ganusov VV, De Boer RJ, (2008) Estimating in vivo death rates of targets due to CD8 T-cell-mediated killing. J Virol 82: 11749-11757.
29. Graw F, Richter K, Oxenius A, Regoes RR, (2011) Comparison of cytotoxic T lymphocyte efficacy in acute and persistent lymphocytic choriomeningitis virus infection. Proc Biol Sci 278: 3395-3402.
30. Regoes RR, Yates A, Antia R, (2007) Mathematical models of cytotoxic T-lymphocyte killing. Immunol Cell Biol 85: 274-279.
31. Barber DL, Wherry EJ, Masopust D, Zhu B, Allison JP, et al. (2006) Restoring function in exhausted CD8 T cells during chronic viral infection. Nature 439: 682-687.
32. Lichterfeld M, Yu XG, Mui SK, Williams KL, Trocha A, et al. (2007) Selective depletion of high-avidity human immunodeficiency virus type 1 (HIV-1)-specific CD8+ T cells after early HIV-1 infection. J Virol 81: 4199-4214.
33. Streeck H, Brumme ZL, Anastario M, Cohen KW, Jolin JS, et al. (2008) Antigen load and viral sequence diversification determine the functional profile of HIV-1-specific CD8+ T cells. PLoS Med 5: e100 doi:10.1371/journal.pmed.0050100.
34. Ogg GS, Jin X, Bonhoeffer S, Dunbar PR, Nowak MA, et al. (1998) Quantitation of HIV-1-specific cytotoxic T lymphocytes and plasma load of viral RNA. Science 279: 2103-2106.
35. Nowak MA, Bangham CR, (1996) Population dynamics of immune responses to persistent viruses. Science 272: 74-79.
36. Asquith B, Bangham CR, (2008) How does HTLV-I persist despite a strong cell-mediated immune response? Trends Immunol 29: 4-11.
37. Addo MM, Yu XG, Rathod A, Cohen D, Eldridge RL, et al. (2003) Comprehensive epitope analysis of human immunodeficiency virus type 1 (HIV-1)-specific T-cell responses directed against the entire expressed HIV-1 genome demonstrate broadly directed responses, but no correlation to viral load. J Virol 77: 2081-2092.
38. Schellens IM, Borghans JA, Jansen CA, De Cuyper IM, Geskus RB, et al. (2008) Abundance of early functional HIV-specific CD8+ T cells does not predict AIDS-free survival time. PLoS ONE 3: e2745 doi:10.1371/journal.pone.0002745.
39. Daucher M, Price DA, Brenchley JM, Lamoreaux L, Metcalf JA, et al. (2008) Virological outcome after structured interruption of antiretroviral therapy for human immunodeficiency virus infection is associated with the functional profile of virus-specific CD8+ T cells. J Virol 82: 4102-4114.
40. Pereyra F, Addo MM, Kaufmann DE, Liu Y, Miura T, et al. (2008) Genetic and immunologic heterogeneity among persons who control HIV infection in the absence of therapy. J Infect Dis 197: 563-571.
41. Borghans JAM, Mølgaard A, de Boer RJ, Kesmir C, (2007) HLA alleles associated with slow progression to AIDS truly prefer to present HIV-1 p24. PLoS ONE 2: e920 doi:10.1371/journal.pone.0000920.
42. Vider-Shalit T, Almani M, Sarid R, Louzoun Y, (2009) The HIV hide and seek game: an immunogenomic analysis of the HIV epitope repertoire. Aids 23: 1311-1318.
43. van Baalen CA, Guillon C, van Baalen M, Verschuren EJ, Boers PH, et al. (2002) Impact of antigen expression kinetics on the effectiveness of HIV-specific cytotoxic T lymphocytes. Eur J Immunol 32: 2644-2652.
44. Schmid BV, Kesmir C, de Boer RJ, (2008) The specificity and polymorphism of the MHC class I prevents the global adaptation of HIV-1 to the monomorphic proteasome and TAP. PLoS ONE 3: e3525 doi:10.1371/journal.pone.0003525.
45. Peters B, Bui H-H, Frankild S, Nielson M, Lundegaard C, et al. (2006) A community resource benchmarking predictions of peptide binding to MHC-I molecules. PLoS Comput Biol 2: e65 doi:10.1371/journal.pcbi.1000048.
46. MacNamara A, Kadolsky U, Bangham CR, Asquith B, (2009) T-cell epitope prediction: rescaling can mask biological variation between MHC molecules. PLoS Comput Biol 5: e1000327 doi:10.1371/journal.pcbi.1000327.
47. Heckerman D, Kadie C, Listgarten J, (2007) Leveraging information across HLA alleles/supertypes improves epitope prediction. J Comput Biol 14: 736-746.
48. MacNamara A, Kadolsky U, Asquith B, (2010) Metaserver, an epitope prediction algorithm. Available:http://web.bioinformatics.ic.ac.uk/metaserver/.
49. Macnamara A, Rowan A, Hilburn S, Kadolsky U, Fujiwara H, et al. (2010) HLA class I binding of HBZ determines outcome in HTLV-1 infection. PLoS Path 6: e1001117 doi:10.1371/journal.ppat.1001117.
50. Rao X, Costa AI, van Baarle D, Kesmir C, (2009) A comparative study of HLA binding affinity and ligand diversity: implications for generating immunodominant CD8+ T cell responses. J Immunol 182: 1526-1532.
51. Kiepiela P, Leslie AJ, Honeyborne I, Ramduth D, Thobakgale C, et al. (2004) Dominant influence of HLA-B in mediating the potential co-evolution of HIV and HLA. Nature 432: 769-775.
52. Mingari MC, Moretta A, Moretta L, (1998) Regulation of KIR expression in human T cells: a safety mechanism that may impair protective T-cell responses. Immunol Today 19: 153-157.
53. Speiser DE, Pittet MJ, Valmori D, Dunbar R, Rimoldi D, et al. (1999) In vivo expression of natural killer cell inhibitory receptors by human melanoma-specific cytolytic T lymphocytes. J Exp Med 190: 775-782.
54. Long EO, Rajagopalan S, (2000) HLA class I recognition by killer cell Ig-like receptors. Semin Immunol 12: 101-108.
55. Ugolini S, Vivier E, (2000) Regulation of T cell function by NK cell receptors for classical MHC class I molecules. Curr Opin Immunol 12: 295-300.
56. Seich Al Basatena NK, Macnamara A, Vine AM, Thio CL, Astemborski J, et al. (2011) KIR2DL2 enhances protective and detrimental HLA class I-mediated immunity in chronic viral infection. PLoS Pathog 7: e1002270 doi:10.1371/journal.ppat.1002270.
57. Kuniholm MH, Kovacs A, Gao X, Xue X, Marti D, et al. (2010) Specific human leukocyte antigen class I and II alleles associated with hepatitis C virus viremia. Hepatology 51: 1514-1522.
58. Thio CL, Gao X, Goedert JJ, Vlahov D, Nelson KE, et al. (2002) HLA-Cw*04 and hepatitis C virus persistence. J Virol 76: 4792-4797.
59. Chuang WC-M, Sarkodie F, Brown CJ, Owusu-Ofori S, Brown J, et al. (2007) Protective effect of HLA-B57 on HCV genotype 2 infection in a West African population. J Virol 79: 724-733.
60. Jeffery KJ, Siddiqui AA, Bunce M, Lloyd AL, Vine AM, et al. (2000) The influence of HLA class I alleles and heterozygosity on the outcome of human T cell lymphotropic virus type I infection. J Immunol 165: 7278-7284.
61. Jeffery KJ, Usuku K, Hall SE, Matsumoto W, Taylor GP, et al. (1999) HLA alleles determine human T-lymphotropic virus-I (HTLV-I) proviral load and the risk of HTLV-I-associated myelopathy. Proc Natl Acad Sci U S A 96: 3848-3853.
62. Khakoo SI, Thio CL, Martin MP, Brooks CR, Gao X, et al. (2004) HLA and NK cell inhibitory receptor genes in resolving hepatitis C virus infection. Science 305: 872-874.
63. Martin MP, Qi Y, Gao X, Yamada E, Martin JN, et al. (2007) Innate partnership of HLA-B and KIR3DL1 subtypes against HIV-1. Nat Genet 39: 733-740.
64. Romero V, Azocar J, Zuniga J, Clavijo OP, Terreros D, et al. (2008) Interaction of NK inhibitory receptor genes with HLA-C and MHC class II alleles in Hepatitis C virus infection outcome. Molecular Immunology 45: 2429-2436.
65. Lopez-Vazquez A, Rodrigo L, Martinez-Borra J, Perez R, Rodriguez M, et al. (2005) Protective effect of the HLA-Bw4I80 epitope and the killer cell immunoglobulin-like receptor 3DS1 gene against the development of hepatocellular carcinoma in patients with hepatitis C virus infection. J Infect Dis 192: 162-165.
66. Martin MP, Gao X, Lee J-H, Nelson GW, Detels R, et al. (2002) Epistatic interaction between KIR3DS1 and HLA-B delays the progression to AIDS. Nat Genet 31: 429-434.
67. Graw F, Regoes RR, (2009) Investigating CTL mediated killing with a 3D cellular automaton. PLoS Comput Biol 5: e1000466 doi:10.1371/journal.pcbi.1000466.
68. Beltman JB, Henrickson SE, von Andrian UH, de Boer RJ, Maree AF, (2009) Towards estimating the true duration of dendritic cell interactions with T cells. J Immunol Methods 347: 54-69.
69. Textor J, (2011) A unified view of T cell recirculation and stochastic search in the lymph node microenvironment [Session 2]. Presented at the International Workshop on T lymphocyte Dynamics in Acute and Chronic Viral Infection, London 2011.
70. Kadolsky UD, Asquith B, (2010) Quantifying the impact of human immunodeficiency virus-1 escape from cytotoxic T-lymphocytes. PLoS Comput Biol 6: e1000981 doi:10.1371/journal.pcbi.1000981.
71. Schmitz JE, Kuroda MJ, Santra S, Sasseville VG, Simon MA, et al. (1999) Control of viremia in simian immunodeficiency virus infection by CD8+ lymphocytes. Science 283: 857-860.
72. Jin X, Bauer DE, Tuttleton SE, Lewin S, Gettie A, et al. (1999) Dramatic rise in plasma viremia after CD8(+) T cell depletion in simian immunodeficiency virus-infected macaques. J Exp Med 189: 991-998.
73. Wong JK, Strain MC, Porrata R, Reay E, Sankaran-Walters S, et al. In vivo CD8+ T-cell suppression of siv viremia is not mediated by CTL clearance of productively infected cells. PLoS Pathog 6: e1000748 doi:10.1371/journal.ppat.1000748.
74. Ho DD, Neumann AU, Perelson AS, Chen W, Leonard JM, et al. (1995) Rapid turnover of plasma virions and CD4 lymphocytes in HIV-1 infection. Nature 373: 123-126.
75. Wei X, Ghosh SK, Taylor ME, Johnson VA, Emini EA, et al. (1995) Viral dynamics in human immunodeficiency virus type 1 infection. Nature 373: 117-122.
76. Althaus CL, De Boer RJ, (2011) Implications of CTL-mediated killing of HIV-infected cells during the non-productive stage of infection. PLoS ONE 6: e16468 doi:10.1371/journal.pone.0016468.
77. Ugolini S, Arpin C, Anfossi N, Walzer T, Cambiaggi A, et al. (2001) Involvement of inhibitory NKRs in the survival of a subset of memory-phenotype CD8+ T cells. Nat Immunol 2: 430-435.
78. Young NT, Uhrberg M, Phillips JH, Lanier LL, Parham P, (2001) Differential expression of leukocyte receptor complex-encoded Ig-like receptors correlates with the transition from effector to memory CTL. J Immunol 166: 3933-3941.
79. Gati A, Guerra N, Gaudin C, Da Rocha S, Escudier B, et al. (2003) CD158 receptor controls cytotoxic t-lymphocyte susceptibility to tumor-mediated activation-induced cell death by interfering with fas signaling. Cancer Res 63: 7475-7482.
80. Cerboni C, Zingoni A, Cippitelli M, Piccoli M, Frati L, et al. (2007) Antigen-activated human T lymphocytes express cell-surface NKG2D ligands via an ATM/ATR-dependent mechanism and become susceptible to autologous NK- cell lysis. Blood 110: 606-615.
81. Soderquest K, Walzer T, Zafirova B, Klavinskis LS, Polic B, et al. (2011) Cutting edge: CD8+ T cell priming in the absence of NK cells leads to enhanced memory responses. J Immunol 186: 3304-3308.
82. Nelson GW, O'Brien SJ, (2006) Using mutual information to measure the impact of multiple genetic factors on AIDS. JAIDS 42: 347-354.
83. Emu B, Sinclair E, Hatano H, Ferre A, Shacklett B, et al. (2008) HLA class I-restricted T-cell responses may contribute to the control of human immunodeficiency virus infection, but such responses are not always necessary for long-term virus control. J Virol 82: 5398-5407.