T lymphocyte responses in HIV-1 infection: Implications for vaccine development

Current Opinion in Immunology

Volumn 11, Issue 4, 1999, Pages 451-459

  Brander, Christian ^a   Walker, Bruce D ^a  

^a MASSACHUSETTS GENERAL HOSPITAL   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

HUMAN IMMUNODEFICIENCY VIRUS VACCINE;

CELLULAR IMMUNITY; CYTOTOXIC T LYMPHOCYTE; HELPER CELL; HUMAN IMMUNODEFICIENCY VIRUS 1; IMMUNOTHERAPY; NONHUMAN; REVIEW; T LYMPHOCYTE; VIREMIA;

EID: 0033179121     PISSN: 09527915     EISSN: None     Source Type: Journal    
DOI: 10.1016/S0952-7915(99)80076-4     Document Type: Article

References (106)

1. Zinkernagel RM, Althage A: Antiviral protection by virus-immune cytotoxic T cells. Infected target cells are lysed before infectious virus progeny is assembled. J Exp Med 1977, 145:644-651.
2. Yang OO, Kalams SA, Rosenzweig M, Trocha A, Jones N, Koziel M, Walker BD, Johnson RP: Efficient lysis of human immunodeficiency virus type 1-infected cells by cytotoxic T lymphocytes. J Virol 1996, 70:5799-5806.
3. Pamer E, Cresswell P: Mechanisms of MHC class I-restricted antigen processing. Annu Rev Immunol 1998, 16:323-358.
4. + lymphocytes. Science 1999, 277:333-338. See annotation [5••].
5. + cells play a crucial role in suppressing SIV replication in vivo.
6. + cell responses.
7. Rosenberg ES, Billingsley JM, Caliendo AM, Boswell SL, Sax PE, Kalams SA, Walker BD: Vigorous HIV-1 specific CD4+ T cell responses associated with control of viremia. Science 1997, 278:1447-1450.
8. Walker BD, Chakrabarti S, Moss B, Paradis TJ, Flynn T, Durno AG, Blumberg RS, Kaplan JC, Hirsch MS, Schooley RT: HIV-specific cytotoxic T lymphocytes in seropositive individuals. Nature 1987, 328:345-348.
9. Plata F, Autran B, Martins LP, Wain HS, Raphael M, Mayaud C, Denis M, Guillon JM, Debre P: AIDS virus-specific cytotoxic T lymphocytes in lung disorders. Nature 1987, 328:348-351.
10. HIV Molecular Immunology Database on World Wide Web URL: http://hiv-web.lanl.gov/immunology/
11. Ogg GS, Dong T, Hansasuta P, Dorrell L, Clarke J, Coker R, Luzzi G, Conlon C, McMichael AP, Rowland-Jones S: Four novel cytotoxic T-lymphocyte epitopes in the highly conserved major homology region of HIV-1 Gag, restricted through B4402, B1801, A2601, B70 (B1509). AIDS 1998, 12:1561-1563.
12. Harrer T, Harrer E, Barbosa P, Kaufmann F, Wagner R, Bruggemann S, Kalden JR, Feinberg M, Johnson RP, Buchbinder S, Walker BD: Recognition of two overlapping CTL epitopes in HIV-1 p17 by CTL from a long-term nonprogressing HIV-1-infected individual. J Immunol 1998, 161:4875-4881.
13. Ikeda-Moore Y, Tomiyama H, Miwa K, Oka S, Iwamoto A, Kaneko Y, Takiguchi M: Identification and characterization of multiple HLA-A24-restricted HIV-1 CTL epitopes: Strong epitopes are derived from V regions of HIV-1. J Immunol 1997, 159:6242-6252.
14. Dong T, Rowland-Jones SL, Fowke KR, Kimani J, Krausa P, Newell H, Blanchard T, Ariyoshi K, Oyugi J, Ngugi E et al.: Cytotoxic T cell responses to multiple conserved HIV epitopes in HIV-resistant prostitutes in Nairobi. J Clin Invest 1998, 102:1758-1765.
15. Haas G, Samri A, Gomard E, Hosmalin A, Duntze J, Bouley JM, Ihlenfeldt HG, Katlama C, Autran B: Cytotoxic T-cell responses to HIV-1 reverse transcriptase, integrase and protease. AIDS 1998, 12:1427-1436.
16. Klein MR, van Baalen CA, Holwerda AM, Kerkhof Garde SR, Bende RJ, Keet IPM, Eeftinck-Schattenkerk JKM, Osterhaus A, Schuitemaker H, Miedema F: Kinetics of Gag-specific cytotoxic T lymphocyte responses during the clinical course of HIV-1 infection: A longitudinal analysis of rapid progressors and long-term asymptomatics. J Exp Med 1995, 181:1356-1372.
17. Carmichael A, Jin X, Sissons P, Borysiewicz L: Quantitative analysis of the human immunodeficiency virus type 1 (HIV-1)-specific cytotoxic T lymphocyte (CTL) response at different stages of HIV-1 infection: Differential CTL responses to HIV-1 and Epstein-Barr virus in late disease. J Exp Med 1993, 177:249-256.
18. Rinaldo C, Huang X-L, Fan ZF, Ding M, Beltz L, Logar A, Panicali D, Mazzara G, Liebmann J, Cottrill M, Gupta P: High levels of antihuman immunodeficiency virus type 1 (HIV-1) memory cytotoxic T-lymphocyte activity and low viral load are associated with lack of disease in HIV-1-infected long-term nonprogressors. J Virol 1995, 69:5838-5842.
19. Wilson JD, Ogg GS, Allen RL, Goulder PJ, Kelleher A, Sewell AK, O'Callaghan CA, Rowland-Jones SL, Callan MF, McMichael AJ: Oligoclonal expansions of CD8(+) T cells in chronic HIV infection are antigen specific. J Exp Med 1998, 188:785-790.
20. Bachelez H, Hadida F, Parizot C, Flageul B, Kemula M, Dubertret L, Debree P, Gorochov G: Oligoclonal expansion of HIV-specific cytotoxic CD8 T lymphocytes in the skin of HIV-1-infected patients with cutaneous pseudolymphoma. J Clin Invest 1998, 101:2506-2516.
21. Quayle AJ, Coston WM, Trocha AK, Kalams SA, Mayer KH, Anderson DJ: Detection of HIV-1-specific CTLs in the semen of HIV-infected individuals. J Immunol 1998, 161:4406-4410.
22. Yang OO, Kalams SA, Trocha A, Cao H, Luster A, Johnson RP, Walker BD: Suppression of human immunodeficiency virus type 1 replication by CD8+ cells: Evidence for HLA class 1-restricted triggering of cytolytic and noncytolytic mechanisms. J Virol 1997, 71:3120-3128.
23. Wagner L, Yang OO, Garcia-Zepeda EA, Ge Y, Kalams SA, Walker BD, Pasternack MS, Luster AD: Beta-chemokines are released from HIV-1-specific cytolytic T-cell granules complexed to proteoglycans. Nature 1998, 391:908-911.
24. Burns JM, Gallo RC, DeVico AL, Lewis GK: A new monoclonal antibody, mAb 4A12, identifies a role for the glycosaminoglycan (GAG) binding domain of RANTES in the antiviral effect against HIV-1 and intracellular Ca2+ signaling. J Exp Med 1998, 188:1917-1927.
25. Oravecz T, Pall M, Wang J, Roderiquez G, Ditto M, Norcross MA: Regulation of anti-HIV-1 activity of RANTES by heparan sulfate proteoglycans. J Immunol 1997, 159:4587-4592.
26. Stranford SA, Skurnick J, Louria D, Osmond D, Chang S, Sninsky J, Ferrari G, Weinhold K, Lindquist C, Levy JA: Lack of infection in HIV-exposed individuals is associated with a strong CD8+ cell noncytotoxic anti-HIV response. Proc Natl Acad Sci USA 1999, 96:1030-1035.
27. Frenkel LM, Mullins JI, Learn GH, Manns-Arcuino L, Herring BL, Kalish ML, Steketee RW, Thea DM, Nichols JE, Liu SL et al.: Genetic evaluation of suspected cases of transient HIV-1 infection of infants. Science 1998, 280:1073-1077.
28. Herr W, Protzer U, Lohse AW, Gerken G, Meyer zum Buschenfelde KH, Wolfel T: Quantification of CD8+ T lymphocytes responsive to human immunodeficiency virus (HIV) peptide antigens in HIV-infected patients and seronegative persons at high risk for recent HIV exposure. J Infect Dis 1998, 178:260-265.
29. Altman JD, Moss P, Goulder PJR, Barouch DH, McHeyzer WMG, Bell JI, McMichael AJ, Davis MM: Phenotypic analysis of antigen-specific T lymphocytes. Science 1996, 274:94-96.
30. Ogg GS, Jin X, Bonhoeffer S, Dunbar PR, Nowak MA, Monard S, Segal JP, Cao Y, Rowland-Jones SL, Cerundolo V et al.: Quantitation of HIV-1-specific cytotoxic T lymphocytes and plasma load of viral RNA. Science 1998, 279:2103-2106. By detecting HIV-1-specific CD8+ cells using tetramer staining, a significant inverse correlation was observed between HIV-specific CTL frequency and plasma RNA viral load. This is the first study that established an association between HIV-1-specific CTLs and viral load.
31. Phillips AN: Reduction of HIV concentration during acute infection: Independence from a specific immune response. Science 1996, 271:497-499.
32. Kalams SA, Walker BD: The critical need for CD4 help in maintaining effective cytotoxic T lymphocyte responses. J Exp Med 1998, 188:2199-2204.
33. Harrer T, Harrer E, Kalams SA, Elbeik T, Staprans SI, Feinberg MB, Cao Y, Ho DD, Yilma T, Caliendo AM et al: Strong cytotoxic T cell and weak neutralizing antibody responses in a subset of persons with stable nonprogressing HIV type 1 infection. AIDS Res Hum Retroviruses 1996, 12:585-592.
34. Borrow P, Lewicki H, Wei X, Horwitz MS, Peffer N, Meyers H, Nelson JA, Gairin JE, Hahn BH, Oldstone MB, Shaw GM: Antiviral pressure exerted by HIV-1-specific cytotoxic T lymphocytes (CTLs) during primary infection demonstrated by rapid selection of CTL escape virus. Nat Med 1997, 3:205-211.
35. Goulder PJ, Phillips RE, Colbert RA, McAdam S, Ogg G, Nowak MA, Giangrande P, Luzzi G, Morgan B, Edwards A et al.: Late escape from an immunodominant cytotoxic T-lymphocyte response associated with progression to AIDS. Nat Med 1997, 3:212-217.
36. Brander C, Hartman KE, Trocha AK, Jones NG, Johnson RP, Korber B, Wentworth P, Buchbinder SP, Wolinsky S, Walker BD, Kalams SA: Lack of strong immune selection pressure by the immunodominant, HLA-A*0201 restricted CTL response in chronic HIV-1 infection. J Clin Invest 1998, 101:2559-2566. Three studies [34,35,36•] focus on different CTL epitopes in HIV-1 gp160 and Gag and compare CTL activity with sequence variation and variant recognition. Whereas the first two reports demonstrate strong selection pressure by these CTLs, the latter study does not confirm these data when the analysis was based on a larger cohort. This may indicate that CTL escape does occur in individual cases but may not be a common phenomenon.
37. Safrit JT, Andrews CA, Zhu T, Ho DD, Koup RA: Characterization of human immunodeficiency virus type 1-specific cytotoxic T lymphocyte clones isolated during acute seroconversion: Recognition of autologous virus sequences within a conserved immunodominant epitope. J Exp Med 1994, 179:463-472.
38. Gray CM, Lawrence J, Schapiro JM, Altman JD, Winters MA, Crompton M, Loi M, Kundu SK, Davis M, Merigan TC: Frequency of class I restricted anti-HIV-1 CD8 T cells in individuals receiving highly active antiretroviral therapy (HAART). J Immunol 1999, 162:1780-1788. Tetramer staining for CTLs specific for epitopes in HIV-1 Gag and reverse transcriptase showed decreased CTL frequency upon HAART mediated suppression of viral replication in asymptomatic patients. Since the majority of tetramer-positive cells killed target cells only after in vitro stimulation, these analyses may detect mainly memory CTLs. These memory CTLs decrease their frequency when antigen becomes limiting under HAART.
39. Birk M, Vahlne A, Sonnerborg A, Sallberg M: Nonsynonymous mutations within the human immunodeficiency virus type 1 p17 gene are clustered to sequences binding to the host human leukocyte antigen class I molecules. AIDS Res Hum Retroviruses 1998, 14:241-248.
40. Wilson C, Brown C, Korber B, Wilkes B, Ruhl D, Sakamotot D, Kunstman K, Luzuriaga K, Hanson C, Widmayer S et al.: Frequent detection of escape from cytotoxic T-lymphocyte recognition in perinatal human immunodeficiency virus (HIV) type 1 transmission: The Ariel project for the prevention of transmission of HIV from mother to infant. J Virol 1999, 73:3975-3985.
41. Lalvani A, Dong T, Ogg G, Patham AA, Newell H, Hill AV, McMichael AJ, Rowland-Jones S: Optimization of a peptide-based protocol employing IL-7 for in vitro restimulation of human cytotoxic T lymphocyte precursors. J Immunol Methods 1997, 210:65-77.
42. Brander C, Goulder PJR, Luzuriaga K, Yang OO, Hartman K, Jones NG, Walker BD, Kalams SA: Persistent HIV-1 specific CTL clonal expansion despite high viral burden post in-utero HIV-1 infection. J Immunol 1999, 162:4796-4800. See annotation [43•].
43. Zajac AJ, Blattman JN, Murali-Krishna K, Sourdive DJ, Suresh M, Altman JD, Ahmed R: Viral immune evasion due to persistence of activated T cells without effector function. J Exp Med 1998, 188:71-82. Both studies [42•,43•], one in humans [42•] and one in mice [43•], suggest the development of inefficient in vivo CTL responses. Whereas the murine study strongly suggests that lack of CD4+ cell help may be responsible for inefficient CTL responses, the human study supports this only indirectly. However, the human study also suggests that clonal exhaustion is not necessarily induced by high viral load.
44. Tan LC, Gudgeon N, Annels NE, Hansasuta P, O'Callaghan CA, Rowland-Jones S, McMichael AJ, Rickinson AB, Callan M: A re-evaluation of the frequency of CD8+ T cells specific for EBV in healthy virus carriers. J Immunol 1999, 162:1827-1835.
45. Kalams SA, Johnson RP, Trocha AK, Dynan MJ, Ngo HS, D'Aquila RT, Kurnick JT, Walker BD: Longitudinal analysis of T cell receptor (TCR) gene usage by human immunodeficiency virus 1 envelope-specific cytotoxic T lymphocyte clones reveals a limited TCR repertoire. J Exp Med 1994, 179:1261-1271.
46. Moss PA, Rowland-Jones SL, Frodsham PM, McAdam S, Giangrande P, McMichael AJ, Bell JI: Persistent high frequency of human immunodeficiency virus-specific cytotoxic T cells in peripheral blood of infected donors. Proc Natl Acad Sci USA 1995, 92:5773-5777.
47. Hay CM, Ruhl DJ, Basgoz N, Wilson CC, Billingsley JM, DePasquale MP, D'Aquila R, Wolinsky S, Crawford JM, Montefiori D, Walker BD: Lack of viral escape and defective in vivo activation of HIV-1-specific CTL in rapidly progressive infection. J Virol 1999, 73:5509-5519.
48. Carrington M, Neslon G, Martin MP, Kissner T, Vlahov D, Goedert JJ, Kaslow R, Buchbinder S, Hoots K, O'Brien SJ: HLA and HIV-1: Heterozygote advantage and B*35-Cw04 disadvantage. Science 1999, 283:1748-1752. This newest study of a series of previous reports of HLA type and disease progression looks at five large cohorts of HIV-1-infected individuals and demonstrates that heterozygosity at the HLA class I locus confers relative resistance to disease progression whereas coexpression of HLA-B35 and -Cw4 accelerates progression. These effects may be linked to CTL activity but NK cell activity is also thought to be of importance.
49. Nelson GW, Kaslow R, Mann DL: Frequency of HLA allele-specific peptide motifs in HIV-1 proteins correlates with the allele's association with relative rates of disease progression after HIV-1 infection. Proc Natl Acad Sci USA 1997, 49:9802-9807.
50. Tang J, COstello C, Keet IP, Rivers C, Leblanc S, Karita E, Allen S, Kaslow RA: HLA class I homozygosity accelerates disease progression in human immunodeficiency virus type 1 infection. AIDS Res Hum Retroviruses 1999, 15:317-324.
51. MacDonald KS, Embree J, Njenga S, Nagelkerke NJ, Ngatia I, Mohammed Z, Barber BH, Ndinya-Achola J, Bwayo J, Plummer FA: Mother-child class I HLA concordance increases perinatal human immunodeficiency virus type 1 transmission. J Infect Dis 1998, 177:551-556.
52. Flamand L, Crowley RW, Lusso P, Colombini-Hatch S, Margolis DM, Gallo RC: Activation of CD8+ T lymphocytes through the T cell receptor turns on CD4 gene expression: Implications for HIV pathogenesis. Proc Natl Acad Sci USA 1998, 95:3111-3116. See annotation [53••].
53. + T cell defects in AIDS patients.
54. Kitchen SG, Korin YD, Roth MD, Landay A, Zack JA: Costimulation of naive CD8(+) lymphocytes induces CD4 expression and allows human immunodeficiency virus type 1 infection. J Virol 1998, 72:9054-9060.
55. Haas G, Plikat U, Debre P, Lucchiari M, Katlama C, Dudoit Y, Bonduelle O, Bauer M, Ihlenfeldt HG, Jung G et al.: Dynamics of viral variants in HIV-1 nef and specific cytotoxic T lymphocytes in vivo. J Immunol 1996, 157:4212-4221.
56. Xu XN, Screaton GR, Gotch FM, McMichael AJ: Evasion of CTL responses by nef-dependent induction of Fas ligand expression on SIV-infected cells. J Exp Med 1997, 186:7-16.
57. Bennett S, Carbone F, Toy T, Miller J, Heath WR: B cells directly tolerize CD8+ T cells. J Exp Med 1998, 188:1977-1983.
58. Herbein G, Mahlknecht U, Batliwalla F, Gregersen P, Pappas T, Butler J, O'Brien WA, Verdin E: Apoptosis of CD8+ T cells is mediated by macrophages through interaction of HIV gp120 with chemokine receptor CXCR4. Nature 1998, 395:189-194.
59. Schwartz O, Marechal V, Le Gall S, Lemonnier F, Heard JM: Endocytosis of major histocompatibility complex class I molecules is induced by the HIV-1 nef protein. Nat Med 1996, 2:338-342.
60. Le Gall S, Erdtmann L, Benichou S, Berlioz-Torrent C, Liu L, Benarous R, Heard JM, Schwartz O: Nef interacts with the mu subunit of clathrin adaptor complexes and reveals a cryptic sorting signal in MHC I molecules. Immunity 1998, 8:483-495. See annotation [61 ••].
61. Collins KL, Chen BK, Kalams SA, Walker BD, Baltimore D: HIV-1 Nef protein protects infected primary cells against killing by cytotoxic T lymphocytes. Nature 1998, 391:397-401. Three reports [59,60••,61 ••] demonstrate the HIV-1-Nef mediated HLA class I downreglation on the surface of cells expressing Nef or infected with HIV-1. This effect depends on a YSQA motif (single-letter code is used for amino acids) found in the cytoplasmic tail of HLA-A and HLA-B molecules but not HLA-C. Therefore, HIV-Nef-expressing cells can escape recognition by CTL clones restricted by HLA-A and -B. Although effective Nef mediated class I downregulation takes longer than the average half-life of HIV-1-infected cells, it may prevent killing of infected cells before progeny virus is released - thereby contributing to a higher level of viremia.
62. Weissman JD, Brown JA, Howcroft TK, Hwang J, Chawla A, Roche PA, Schiltz L, Nakatani Y, Singer DS: HIV-1 tat binds TAFII250 and represses TAFII250-dependent transcription of major histocompatibility class I genes. Proc Natl Acad Sci USA 1998, 95:11601-11606.
63. Zocchi MR, Rubartelli A, Morgavi P, Poggi A: HIV-1 Tat inhibits human natural killer cell function by blocking L-type calcium channels. J Immunol 1998, 161:2938-2943.
64. Autran B, Carcelain G, Li TS, Blanc C, Mathez D, Tubiana R, Katlama C, Debre P, Leibowitch J: Positive effects of combined antiretroviral therapy on CD4+ T cell homeostasis and function in advanced HIV disease. Science 1997, 277:112-116.
65. Li TS, Tubiana R, Katlama C, Calvez V, Ait-Mohand H, Autran B: Long-lasting recovery in CD4 T-cell function and viral-load reduction after highly active antiretroviral therapy in advanced HIV-1 disease. Lancet 1998, 351:1682-1686.
66. Magierowska M, Theodorou I, Debre P, Sanson F, Autran B, Riviere Y, Charron D, Costagliola D: Combined genotypes of CCR5, CCR2, SDF1, and HLA genes can predict the long-term nonprogressor status in human immunodeficiency virus-1-infected individuals. Blood 1999, 93:936-941.
67. + T cell responses were restored in these patients upon HAART.
68. Macdonald JC, Torriani FJ, Morse LS, Karavellas MR Reed JB, Freeman WR: Lack of reactivation of cytomegalovirus (CMV) retinitis after stopping CMV maintenance therapy in AIDS patients with sustained elevations in CD4 T cells in response to highly active antiretroviral therapy. J Infect Dis 1998, 177:1182-1187.
69. Bisset LR, Cone RW, Huber W, Battegay M, Vernazza PL, Weber R, Grob PJ, Opravil M: Highly active antiretroviral therapy during early HIV infection reverses T-cell activation and maturation abnormalities. AIDS 1998, 12:2115-2123.
70. Zhang ZQ, Notermans DW, Sedgewick G, Cavert W, Wietgrefe S, Zupancic M, Gebhard K, Henry K, Boies L, Chen Z et al.: Kinetics of CD4+ T cell repopulation of lymphoid tissues after treatment of HIV-1 infection. Proc Natl Acad Sci USA 1998, 95:1154-1159.
71. David D, Bani L, Moreau JL, Treilhou MP, Nakarai T, Joussemet M, Ritz J, Dupont B, Pialoux G, Theze J: Regulatory dysfunction of the interleukin-2 receptor during HIV infection and the impact of triple combination therapy. Proc Natl Acad Sci USA 1998, 95:11348-11353.
72. + cell repertoire was observed in individuals who responded well to antiviral therapy.
73. Lederman MM, Connick E, Landay A, Kuritzkes DR, Spritzler J, St Clair M, Kotzin BL, Fox L, Chiozzi MH, Leonard JM et al.: Immunologic responses associated with 12 weeks of combination antiretroviral therapy consisting of zidovudine, lamivudine, and ritonavir: Results of AIDS clinical trials group protocol 315. J Infect Dis 1998, 178:70-79.
74. Kelleher AD, Carr A, Zaunders J, Cooper DA: Alterations in the immune response of human immunodeficiency virus (HIV)-infected subjects treated with an HIV-specific protease inhibitor, ritonavir. J Infect Dis 1996, 173:321-329.
75. Markowitz M, Vesanen M, Tenner-Racz K, Cao Y, Binley JM, Talal A, Hurley A, Ji X, Chaudhry MR, Yaman M et al.: The effect of commencing combination antiretroviral therapy soon after human immunodeficiency virus type 1 infection on viral replication and antiviral immune responses. J Infect Dis 1999, 179:527-536.
76. Douek DC, McFraland R, Keiser P, Gage EA, Massey J, Haynes B, Polis MA, Haase A, Feinberg M, Sullivan JL et al.: Changes in thymic function with age and during the treatment of HIV infection. Nature 1998, 396:690-695. By detecting excised DNA products after TCR rearrangement, this elegant study demonstrates that adult thymus is able to produce new naive cells. In HIV-1-infected individuals undergoing HAART, the authors find a rapid increase in thymic output of naive cells - indicating that adult thymus can contribute to immune reconstitution upon HAART.
77. Rosenberg ES, Walker BD: HIV type 1-specific helper T cells: A critical host defense. AIDS Res Hum Retroviruses 1998, 14:S143-S147.
78. Ogg G, Jin X, Bonhoeffer S, Moss P, Nowak M, Monard S, Segal J, Cao Y, Rowland-Jones S, Hurley A et al.: Decay kinetics of human immunodeficiency virus-specific effector cytotoxic T lymphocytes after combination antiretroviral therapy. J Virol 1999, 73:797-800. This report investigates the fate of HIV-1-specific CTLs in patients undergoing HAART. Tetramer staining of CTLs shows early rapid fluctuations in the HIV-1-specific CTL response within the first two weeks after onset of HAART, followed by an exponential decay of HIV-1-specific CTLs with a half-life of 45 days.
79. Andre P, Groettrup M, Klenerman P, de Giuli R, Booth BL Jr, Cerundolo V, Bonneville M, Jotereau F, Zinkernagel RM, Lotteau V: An inhibitor of HIV-1 protease modulates proteasome activity, antigen presentation, and T cell responses. Proc Natl Acad Sci USA 1998, 95:13120-13124.
80. Schwartz O, Marechal V, Friguet B, Arenzana-Seisdedos F, Heard JM: Antiviral activity of the proteasome on incoming human immunodeficiency virus type 1. J Virol 1998, 72:3845-3850.
81. Corey L, McElrath MJ, Weinhold K, Matthews T, Stablein D, Graham B, Keefer M, Schwartz D, Gorse G: Cytotoxic T cell and neutralizing antibody responses to human immunodeficiency virus type 1 envelope with a combination vaccine regimen. AIDS Vaccine Evaluation Group. J Infect Dis 1998, 177:301-309.
82. Clements-Mann ML, Weinhold K, Matthews TJ, Graham BS, Gorse GJ, Keefer MC, McElrath MJ, Hsieh RH, Mestecky J, Zolla-Pazner S et al.: Immune responses to human immunodeficiency virus (HIV) type 1 induced by canarypox expressing HIV-1MN gp120, HIV-1SF2 recombinant gp120, or both vaccines in seronegative adults. NIAID AIDS Vaccine Evaluation Group. J Infect Dis 1998, 177:1230-1246.
83. Joag SV, Liu ZQ, Stephens EB, Smith MS, Kumar A, Li Z, Wang C, Sheffer D, Jia F, Foresman L et al.: Oral immunization of macaques with attenuated vaccine virus induces protection against vaginally transmitted AIDS. J Virol 1998, 72:9069-9078.
84. Baba TW, Liska V, Khimani AH, Ray NB, Dailey PJ, Penninck D, Bronson R, Greene MF, McClure HM, Martin LN, Ruprecht RM: Live attenuated, multiply deleted simian immunodeficiency virus causes AIDS in infant and adult macaques. Nat Med 1999, 5:194-203. Despite multiple deletions in the genome of this mutant SIV used as an attenuated vaccine, the majority (75%) of vaccinated infant macaques developed AIDS. Four out of sixteen vaccinated adult animals also showed resurgence of chronic viremia. These studies warn that human AIDS vaccines built on similar prototypes may cause AIDS.
85. Belyakov IM, Wyatt LS, Ahlers JD, Earl P, Pendleton CD, Kelsall BL, Strober W, Moss B, Berzofsky JA: Induction of a mucosal cytotoxic T-lymphocyte response by intrarectal immunization with a replication-deficient recombinant vaccinia virus expressing human immunodeficiency virus 89.6 envelope protein. J Virol 1998, 72:8264-8272.
86. Sasaki S, Sumino K, Hamajima K, Fukushima J, Ishii N, Kawamoto S, Mohri H, Kensil CR, Okuda K: Induction of systemic and mucosal immune responses to human immunodeficiency virus type 1 by a DNA vaccine formulated with QS-21 saponin adjuvant via intramuscular and intranasal routes. J Virol 1998, 72:4931-4939.
87. Benson J, Chougnet C, Robert-Guroff M, Montefiori D, Markham P, Shearer G, Gallo RC, Cranage M, Paoletti E, Limbach K et al.: Recombinant vaccine-induced protection against the highly pathogenic simian immunodeficiency virus SIV(mac251): Dependence on route of challenge exposure. J Virol 1998, 72:4170-4182.
88. Barouch DH, Santra S, Steenbeke TD, Zheng XX, Perry HC, Davies ME, Freed DC, Craiu A, Strom TB, Shiver JW, Letvin NL: Augmentation and suppression of Immune Responses to an HIV-1 DNA vaccine by plasmid cytokine/Ig administration. J Immunol 1998, 161:1875-1882.
89. Seth A, Ourmanov I, Kuroda MJ, Schmitz JE, Carroll MW, Wyatt LS, Moss B, Forman MA, Hirsch VM, Letvin NL: Recombinant modified vaccinia virus Ankara-simian immunodeficiency virus gag pol elicits cytotoxic T lymphocytes in rhesus monkeys detected by a major histocompatibility complex class I/peptide tetramer. Proc Natl Acad Sci USA 1998, 95:10112-10116.
90. Connor RI, Korber BT, Graham BS, Hahn BH, Ho DD, Walker BD, Neumann AU, Vermund SH, Mestecky J, Jackson S et al.: Immunological and virological analyses of persons infected by human immunodeficiency virus type 1 while participating in trials of recombinant gp120 subunit vaccines. J Virol 1998, 72:1552-1576.
91. Mortara L, Letourneur F, Gras-Masse H, Venet A, Guillet JG, Bourgault-Villada I: Selection of virus variants and emergence of virus escape mutants after immunization with an epitope vaccine. J Virol 1998, 72:1403-1410.
92. Hislop AD, Good MF, Mateo L, Gardner J, Gatei MH, Daniel RC, Meyers BV, Lavin MF, Suhrbier A: Vaccine-induced cytotoxic T lymphocytes protect against retroviral challenge. Nat Med 1998, 4:1193-1196. This study demonstrates that peptide vaccination with a minimal ovine CTL peptide epitope of the bovine leukemia retrovirus in incomplete Freund's adjuvant protects sheep from viral challenge. The limited sequence variation in this retrovirus indicates that in the absence of CTL escape variants, virus-specific CTLs targeting a single epitope are able to prevent the establishment of a latent retroviral infection.
93. Cao H, Kanki P, Sankale JL, Dieng-Sarr A, Mazzara GP, Kalams SA, Korber B, Mboup S, Walker BD: Cytotoxic T-lymphocyte cross-reactivity among different human immunodeficiency virus type 1 clades: Implications for vaccine development. J Virol 1997, 71:8615-8623.
94. Lynch JA, deSouza M, Robb MD, Markowitz L, Nitayaphan S, Sapan CV, Mann DL, Birx DL, Cox JH: Cross-clade cytotoxic T cell response to human immunodeficiency virus type 1 proteins among HLA disparate North Americans and Thais. J Infect Dis 1998, 178:1040-1046. See annotation [97•].
95. Wilson SE, Pedersen SL, Kunich JC, Wilkins VL, Mann DL, Mazzara GP, Tartaglia J, Celum CL, Sheppard HW: Cross-clade envelope glycoprotein 160-specific CD8+ cytotoxic T lymphocyte responses in early HIV type 1 clade B infection. AIDS Res Hum Retroviruses 1998, 14:925-937. See annotation [97•].
96. McAdam S, Kaleebu P, Krausa P, Goulder P, French N, Collin B, Blanchard T, Whitworth J, McMichael A, Gotch F: Cross-clade recognition of p55 by cytotoxic T lymphocytes in HIV-1 infection. AIDS 1998, 12:571-579. See annotation [97•].
97. Bertoletti A, Cham F, McAdam S, Rostron T, Rowland-Jones S, Sabally S, Corrah T, Ariyoshi K, Whittle H: Cytotoxic T cells from human immunodeficiency virus type 2-infected patients frequently cross-react with different human immunodeficiency virus type 1 clades. J Virol 1998, 72:2439-2448. Five reports [93,94•-97•] document cross-clade recognition of HIV CTL epitopes. Whereas one study [97•] shows that a large proportion of HIV-2-infected individuals possess cytotoxic T cell responses which are able to recognize HIV-1 proteins, the other reports focus on the cross-recognition of epitopes in Gag, Pol, Nef and Env proteins derived from different HIV-1 clades. Despite that, the development of an HIV vaccine capable of recognizing diverse HIV clades will be problematic. Population specific CTL data are needed to adequately prepare for vaccine trials outside of North America and Europe.
98. Thomson SA, Sherritt MA, Medveczky J, Elliott SL, Moss DJ, Fernando GJ, Brown LE, Suhrbier A: Delivery of multiple CD8 cytotoxic T cell epitopes by DNA vaccination. J Immunol 1998, 160:1717-1723.
99. Bartlett JA, Wasserman SS, Hicks CB, Dodge RT, Weinhold KJ, Tacket CO, Ketter N, Wittek AE, Palker TJ, Haynes BF: Safety and immunogenicity of an HLA-based HIV envelope polyvalent synthetic peptide immunogen. DATRI 010 Study Group. Division of AIDS Treatment Research Initiative. AIDS 1998, 12:1291-1300.
100. Tobery T, Siliciano RF: Induction of enhanced CTL-dependent protective immunity in vivo by N-end rule targeting of a model tumor antigen. J Immunol 1999, 162:639-642.
101. Leandersson AC, Bratt G, Hinkula J, Gilljam G, Cochaux P, Samson M, Sandstrom E, Wahren B: Induction of specific T-cell responses in HIV infection. AIDS 1998, 12:157-166.
102. Kelleher AD, Roggensack M, Jaramillo AB, Smith DE, Walker A, Gow I, McMurchie M, Harris J, Patou G, Cooper DA: Safety and immunogenicity of a candidate therapeutic vaccine, p24 virus-like particle, combined with zidovudine, in asymptomatic subjects. Community HIV Research Network Investigators. AIDS 1998, 12:175-182.
103. Kundu SK, Engleman E, Benike C, Shapero MH, Dupuis M, van Schooten WC, Eibl M, Merigan TC: A pilot clinical trial of HIV antigen-pulsed allogeneic and autologous dendritic cell therapy in HIV-infected patients. AIDS Res Hum Retroviruses 1998, 14:551-560.
104. Chun TW, Engel D, Berrey MM, Shea T, Corey L, Fauci AS: Early establishment of a pool of latently infected, resting CD4(+) T cells during primary HIV-1 infection. Proc Natl Acad Sci USA 1998, 95:8869-8873. See annotation [105••].
105. + T cells and that virus could be completely eradicated with HAART; this has to be considered in deciding whether to terminate treatment in patients who respond to HAART.
106. Kalams SA, Buchbinder SP, Rosenberg ES, Billingsley JM, Colbert DS, Jones NG, Shea AK, Trocha AK, Walker BD: Association between virus-specific CTL and helper responses in HIV-1 infection. J Virol 1999, in press.