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J Virol. 1994 Sep; 68(9): 6103–6110.
PMCID: PMC237022

Virus-specific CD8+ cytotoxic T-lymphocyte activity associated with control of viremia in primary human immunodeficiency virus type 1 infection.

Abstract

Human immunodeficiency virus type 1 (HIV-1) Env-, Gag-, Pol-, Nef-, and Tat-specific cytotoxic T-lymphocyte (CTL) activities were quantitated temporally in five patients with symptomatic primary HIV-1 infection. A dominant CD8(+)-mediated, major histocompatibility complex class I-restricted CTL response to the HIV-1 envelope glycoprotein, gp160, was noted in four of the five patients studied. The level of HIV-1-specific CTL activity in the five patients paralleled the efficiency of control of primary viremia. Patients who mounted strong gp160-specific CTL responses showed rapid reduction of acute plasma viremia and antigenemia, while in contrast, primary viremia and antigenemia were poorly controlled in patients in whom virus-specific CTL activity was low or undetectable. These results suggest that HIV-1-specific CTL activity is a major component of the host immune response associated with the control of virus replication following primary HIV-1 infection and have important implications for the design of antiviral vaccines.

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  • Ariyoshi K, Harwood E, Chiengsong-Popov R, Weber J. Is clearance of HIV-1 viraemia at seroconversion mediated by neutralising antibodies? Lancet. 1992 Nov 21;340(8830):1257–1258. [PubMed]
  • Auger I, Thomas P, De Gruttola V, Morse D, Moore D, Williams R, Truman B, Lawrence CE. Incubation periods for paediatric AIDS patients. Nature. 1988 Dec 8;336(6199):575–577. [PubMed]
  • Byrne JA, Oldstone MB. Biology of cloned cytotoxic T lymphocytes specific for lymphocytic choriomeningitis virus: clearance of virus in vivo. J Virol. 1984 Sep;51(3):682–686. [PMC free article] [PubMed]
  • Chakrabarti S, Brechling K, Moss B. Vaccinia virus expression vector: coexpression of beta-galactosidase provides visual screening of recombinant virus plaques. Mol Cell Biol. 1985 Dec;5(12):3403–3409. [PMC free article] [PubMed]
  • Cheingsong-Popov R, Panagiotidi C, Bowcock S, Aronstam A, Wadsworth J, Weber J. Relation between humoral responses to HIV gag and env proteins at seroconversion and clinical outcome of HIV infection. BMJ. 1991 Jan 5;302(6767):23–26. [PMC free article] [PubMed]
  • Clark SJ, Saag MS, Decker WD, Campbell-Hill S, Roberson JL, Veldkamp PJ, Kappes JC, Hahn BH, Shaw GM. High titers of cytopathic virus in plasma of patients with symptomatic primary HIV-1 infection. N Engl J Med. 1991 Apr 4;324(14):954–960. [PubMed]
  • Claverie JM, Kourilsky P, Langlade-Demoyen P, Chalufour-Prochnicka A, Dadaglio G, Tekaia F, Plata F, Bougueleret L. T-immunogenic peptides are constituted of rare sequence patterns. Use in the identification of T epitopes in the human immunodeficiency virus gag protein. Eur J Immunol. 1988 Oct;18(10):1547–1553. [PubMed]
  • Clerici M, Berzofsky JA, Shearer GM, Tacket CO. Exposure to human immunodeficiency virus (HIV) type I indicated by HIV-specific T helper cell responses before detection of infection by polymerase chain reaction and serum antibodies [corrected]. J Infect Dis. 1991 Jul;164(1):178–182. [PubMed]
  • Clerici M, Giorgi JV, Chou CC, Gudeman VK, Zack JA, Gupta P, Ho HN, Nishanian PG, Berzofsky JA, Shearer GM. Cell-mediated immune response to human immunodeficiency virus (HIV) type 1 in seronegative homosexual men with recent sexual exposure to HIV-1. J Infect Dis. 1992 Jun;165(6):1012–1019. [PubMed]
  • Daar ES, Moudgil T, Meyer RD, Ho DD. Transient high levels of viremia in patients with primary human immunodeficiency virus type 1 infection. N Engl J Med. 1991 Apr 4;324(14):961–964. [PubMed]
  • Earl PL, Hügin AW, Moss B. Removal of cryptic poxvirus transcription termination signals from the human immunodeficiency virus type 1 envelope gene enhances expression and immunogenicity of a recombinant vaccinia virus. J Virol. 1990 May;64(5):2448–2451. [PMC free article] [PubMed]
  • Earl PL, Koenig S, Moss B. Biological and immunological properties of human immunodeficiency virus type 1 envelope glycoprotein: analysis of proteins with truncations and deletions expressed by recombinant vaccinia viruses. J Virol. 1991 Jan;65(1):31–41. [PMC free article] [PubMed]
  • Falkner FG, Fuerst TR, Moss B. Use of vaccinia virus vectors to study the synthesis, intracellular localization, and action of the human immunodeficiency virus trans-activator protein. Virology. 1988 Jun;164(2):450–457. [PubMed]
  • Flexner C, Broyles SS, Earl P, Chakrabarti S, Moss B. Characterization of human immunodeficiency virus gag/pol gene products expressed by recombinant vaccinia viruses. Virology. 1988 Oct;166(2):339–349. [PubMed]
  • Hoffenbach A, Langlade-Demoyen P, Dadaglio G, Vilmer E, Michel F, Mayaud C, Autran B, Plata F. Unusually high frequencies of HIV-specific cytotoxic T lymphocytes in humans. J Immunol. 1989 Jan 15;142(2):452–462. [PubMed]
  • Johnson RP, Trocha A, Buchanan TM, Walker BD. Identification of overlapping HLA class I-restricted cytotoxic T cell epitopes in a conserved region of the human immunodeficiency virus type 1 envelope glycoprotein: definition of minimum epitopes and analysis of the effects of sequence variation. J Exp Med. 1992 Apr 1;175(4):961–971. [PMC free article] [PubMed]
  • Kannagi M, Masuda T, Hattori T, Kanoh T, Nasu K, Yamamoto N, Harada S. Interference with human immunodeficiency virus (HIV) replication by CD8+ T cells in peripheral blood leukocytes of asymptomatic HIV carriers in vitro. J Virol. 1990 Jul;64(7):3399–3406. [PMC free article] [PubMed]
  • Karacostas V, Nagashima K, Gonda MA, Moss B. Human immunodeficiency virus-like particles produced by a vaccinia virus expression vector. Proc Natl Acad Sci U S A. 1989 Nov;86(22):8964–8967. [PMC free article] [PubMed]
  • Koenig S, Earl P, Powell D, Pantaleo G, Merli S, Moss B, Fauci AS. Group-specific, major histocompatibility complex class I-restricted cytotoxic responses to human immunodeficiency virus 1 (HIV-1) envelope proteins by cloned peripheral blood T cells from an HIV-1-infected individual. Proc Natl Acad Sci U S A. 1988 Nov;85(22):8638–8642. [PMC free article] [PubMed]
  • Koenig S, Fuerst TR, Wood LV, Woods RM, Suzich JA, Jones GM, de la Cruz VF, Davey RT, Jr, Venkatesan S, Moss B, et al. Mapping the fine specificity of a cytolytic T cell response to HIV-1 nef protein. J Immunol. 1990 Jul 1;145(1):127–135. [PubMed]
  • Koup RA, Sullivan JL, Levine PH, Brettler D, Mahr A, Mazzara G, McKenzie S, Panicali D. Detection of major histocompatibility complex class I-restricted, HIV-specific cytotoxic T lymphocytes in the blood of infected hemophiliacs. Blood. 1989 May 15;73(7):1909–1914. [PubMed]
  • Littaua RA, Oldstone MB, Takeda A, Debouck C, Wong JT, Tuazon CU, Moss B, Kievits F, Ennis FA. An HLA-C-restricted CD8+ cytotoxic T-lymphocyte clone recognizes a highly conserved epitope on human immunodeficiency virus type 1 gag. J Virol. 1991 Aug;65(8):4051–4056. [PMC free article] [PubMed]
  • McChesney M, Tanneau F, Regnault A, Sansonetti P, Montagnier L, Kieny MP, Rivière Y. Detection of primary cytotoxic T lymphocytes specific for the envelope glycoprotein of HIV-1 by deletion of the env amino-terminal signal sequence. Eur J Immunol. 1990 Jan;20(1):215–220. [PubMed]
  • McMichael AJ, Gotch FM, Noble GR, Beare PA. Cytotoxic T-cell immunity to influenza. N Engl J Med. 1983 Jul 7;309(1):13–17. [PubMed]
  • Merson MH. Slowing the spread of HIV: agenda for the 1990s. Science. 1993 May 28;260(5112):1266–1268. [PubMed]
  • Mosier DE, Gulizia RJ, MacIsaac PD, Corey L, Greenberg PD. Resistance to human immunodeficiency virus 1 infection of SCID mice reconstituted with peripheral blood leukocytes from donors vaccinated with vaccinia gp160 and recombinant gp160. Proc Natl Acad Sci U S A. 1993 Mar 15;90(6):2443–2447. [PMC free article] [PubMed]
  • Nixon DF, McMichael AJ. Cytotoxic T-cell recognition of HIV proteins and peptides. AIDS. 1991 Sep;5(9):1049–1059. [PubMed]
  • Phillips RE, Rowland-Jones S, Nixon DF, Gotch FM, Edwards JP, Ogunlesi AO, Elvin JG, Rothbard JA, Bangham CR, Rizza CR, et al. Human immunodeficiency virus genetic variation that can escape cytotoxic T cell recognition. Nature. 1991 Dec 12;354(6353):453–459. [PubMed]
  • Piatak M, Jr, Saag MS, Yang LC, Clark SJ, Kappes JC, Luk KC, Hahn BH, Shaw GM, Lifson JD. High levels of HIV-1 in plasma during all stages of infection determined by competitive PCR. Science. 1993 Mar 19;259(5102):1749–1754. [PubMed]
  • Plata F, Autran B, Martins LP, Wain-Hobson S, Raphaël M, Mayaud C, Denis M, Guillon JM, Debré P. AIDS virus-specific cytotoxic T lymphocytes in lung disorders. Nature. 1987 Jul 23;328(6128):348–351. [PubMed]
  • Quinnan GV, Jr, Kirmani N, Rook AH, Manischewitz JF, Jackson L, Moreschi G, Santos GW, Saral R, Burns WH. Cytotoxic t cells in cytomegalovirus infection: HLA-restricted T-lymphocyte and non-T-lymphocyte cytotoxic responses correlate with recovery from cytomegalovirus infection in bone-marrow-transplant recipients. N Engl J Med. 1982 Jul 1;307(1):7–13. [PubMed]
  • Reimann KA, Tenner-Racz K, Racz P, Montefiori DC, Yasutomi Y, Lin W, Ransil BJ, Letvin NL. Immunopathogenic events in acute infection of rhesus monkeys with simian immunodeficiency virus of macaques. J Virol. 1994 Apr;68(4):2362–2370. [PMC free article] [PubMed]
  • Riviere Y, Tanneau-Salvadori F, Regnault A, Lopez O, Sansonetti P, Guy B, Kieny MP, Fournel JJ, Montagnier L. Human immunodeficiency virus-specific cytotoxic responses of seropositive individuals: distinct types of effector cells mediate killing of targets expressing gag and env proteins. J Virol. 1989 May;63(5):2270–2277. [PMC free article] [PubMed]
  • 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 Feb 1;179(2):463–472. [PMC free article] [PubMed]
  • Sethi KK, Omata Y, Schneweis KE. Protection of mice from fatal herpes simplex virus type 1 infection by adoptive transfer of cloned virus-specific and H-2-restricted cytotoxic T lymphocytes. J Gen Virol. 1983 Feb;64(Pt 2):443–447. [PubMed]
  • Tsubota H, Lord CI, Watkins DI, Morimoto C, Letvin NL. A cytotoxic T lymphocyte inhibits acquired immunodeficiency syndrome virus replication in peripheral blood lymphocytes. J Exp Med. 1989 Apr 1;169(4):1421–1434. [PMC free article] [PubMed]
  • Tyler DS, Nastala CL, Stanley SD, Matthews TJ, Lyerly HK, Bolognesi DP, Weinhold KJ. GP120 specific cellular cytotoxicity in HIV-1 seropositive individuals. Evidence for circulating CD16+ effector cells armed in vivo with cytophilic antibody. J Immunol. 1989 Feb 15;142(4):1177–1182. [PubMed]
  • 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 Jul 23;328(6128):345–348. [PubMed]
  • Walker BD, Flexner C, Birch-Limberger K, Fisher L, Paradis TJ, Aldovini A, Young R, Moss B, Schooley RT. Long-term culture and fine specificity of human cytotoxic T-lymphocyte clones reactive with human immunodeficiency virus type 1. Proc Natl Acad Sci U S A. 1989 Dec;86(23):9514–9518. [PMC free article] [PubMed]
  • Walker BD, Plata F. Cytotoxic T lymphocytes against HIV. AIDS. 1990 Mar;4(3):177–184. [PubMed]
  • Walker CM, Moody DJ, Stites DP, Levy JA. CD8+ lymphocytes can control HIV infection in vitro by suppressing virus replication. Science. 1986 Dec 19;234(4783):1563–1566. [PubMed]
  • Yap KL, Ada GL, McKenzie IF. Transfer of specific cytotoxic T lymphocytes protects mice inoculated with influenza virus. Nature. 1978 May 18;273(5659):238–239. [PubMed]
  • Yasutomi Y, Reimann KA, Lord CI, Miller MD, Letvin NL. Simian immunodeficiency virus-specific CD8+ lymphocyte response in acutely infected rhesus monkeys. J Virol. 1993 Mar;67(3):1707–1711. [PMC free article] [PubMed]

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