HIV-2-SPECIFIC CYTOTOXIC T-LYMPHOCYTE ACTIVITY IS INVERSELY RELATED TO PROVIRAL LOAD

被引：36

作者：

ARIYOSHI, K ^{[1
]}

CHAM, F ^{[1
]}

BERRY, N ^{[1
]}

JAFFAR, S ^{[1
]}

SABALLY, S ^{[1
]}

CORRAH, T ^{[1
]}

WHITTLE, H ^{[1
]}

机构：

[1] UCL, SCH MED, DIV VIROL, LONDON W1N 8AA, ENGLAND

来源：

AIDS | 1995年 / 9卷 / 06期

关键词：

HIV-2; CYTOTOXIC T LYMPHOCYTES; VIRAL LOAD;

D O I：

10.1097/00002030-199506000-00004

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

100102 ;

摘要：

Objectives: To characterize HIV-specific cytotoxic T-lymphocyte (CTL) activiti Methods: Peripheral blood mononuclear cells were collected from 16 HIV-2-seropositive and four HIV-1/-2 dually seropositive subjects. CTL were restimulated with autologous phytohaemagglutinin-stimulated blasts and CTL activities in 'bulk' cultures were evaluated 7 and 14 days later by a standard Cr-51-release assay using autologous B-cell lines infected with recombinant vaccinia expressing HIV-2 Gag, Pol or Nef protein. Proviral load was quantified by polymerase chain reaction (PCR) which used HIV-2 long terminal repeat primers and an external standard control made by an HIV-2(CBL-22) chronically infected C8166 cell line. A biotinylated primer was used to capture the S-35 dATP-incorporated secondary PCR product in a quantitative radiometric assay. Results: After 14 days of culture CTL responses against Gag or Pol protein were seen in 18 (90.0%) and 14 (70.0%) out of 20 subjects, respectively, whereas a CTL response was noted against Nef protein in five (25.0%) out of 20 subjects. In 14 (70.0%) out of 20 subjects multiple HIV proteins were simultaneously recognized. The sum of specific lysis (%) against HIV-2 Gag, Pol and Nef at 30:1 effector-to-target ratio, or specific lysis of the dominant CTL response, correlated strongly with HIV-2 proviral load expressed as copies per 10(5) CD4+ cells (r=-0.625, P=0.003 and r=-0.674, P=0.001, respectively). Conclusion: HIV-2-specific CTL to multiple gene products was demonstrated in most HIV-2-infected individuals. An inverse correlation between the level of CTL activity and proviral load was found, which supports the hypothesis that CTL are important in the control of HIV-2 replication.

引用

页码：555 / 559

页数：5

共 20 条

[1] McMichael A.J., Walker B.D., Cytotoxic T lymphocyte epitopes: Implications for HIV vaccines, AIDS, 8, 1 SUPPL., (1994)
[2] Zinkernagel R.M., Hengartner H., T-cell-mediated immunopathology versus direct cytolysis by virus: Implications for HIV and AIDS, Immunol Today, 15, pp. 262-268, (1994)
[3] Walker B.D., Flexner C., Paradis T.J., Et al., HIV-1 reverse transcriptase is a target for cytotoxic T lymphocytes in infected individuals, Science, 240, pp. 64-65, (1988)
[4] Nixon D.F., Townsend A.R.M., Elvin J.C., Rizza C.R., Gallwey J., McMichael A.J., HIV-1 Gag-specific cytotoxic T lymphocytes defined with recombinant vaccinia virus and synthetic peptides, Nature, 336, pp. 484-487, (1988)
[5] Lamhamedi-Cherradi S., Culmann-Penciolelli B., Guy B., Et al., Qualitative and quantitative analysis of human cytotoxic T-lymphocyte responses to HIV-1 proteins, AIDS, 6, pp. 1249-1258, (1992)
[6] Gotch F.M., Nixon D.F., Alp N., McMichael A.J., Borysiewicz L.K., High frequency of memory and effector Gag-specific cytotoxic T lymphocytes in HIV-seropositive individuals, Int Immunol, 2, pp. 707-712, (1990)
[7] Carmichael A., Jin X., Sissons P., Borysiewicz L., Quantitative analysis of the human immunodeficiency virus type (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, 177, pp. 249-256, (1993)
[8] Koup R.A., Safrit J.T., Cao Y., Et al., Temporal association of cellular immune responses with the initial control of viraemia in primary human immunodeficiency virus type 1 syndrome, J Virol, 68, pp. 4650-4655, (1994)
[9] Borrow P., Lewicki H., Hahn B.H., Shaw G.M., Oldstone M.B., Virus-specific CD8+ cytotoxic T-lymphocyte activity associated with control of viremia in primary human immunodeficiency virus type 1 infection, J Virol, 68, pp. 6103-6110, (1994)
[10] Kundu S.K., Merigan T.C., Relationship of HIV-1 provirus load, CD8+ CD11+ T cells and HIV-1 envelope-specific cytotoxic T lymphocytes in HIV-infected asymptomatic patients, Immunology, 83, pp. 81-85, (1994)

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