Abstract
CD8+ (suppressor/cytotoxic) lymphocytes block replication of HIV-1 or the simian immunodeficiency virus of macaques (SIVmac) in PBL of infected individuals. We now show that these CD8+ lymphocytes undergo clonal expansion in vivo after AIDS virus infection of the individual, suggesting they may be antigen-specific T cells. These CD8+ cells block replication of virus in autologous but not MHC class I-mismatched PBL. The inhibitory lymphocytes express the integrin family molecule 4B4 and the CTL-associated S6F1 epitope of LFA-1. Finally, physical contact is required for the CD8+ lymphocyte-mediated inhibition of AIDS virus replication, since this inhibitory function is blocked by anti-LFA-1 and anti-CD8 mAbs. These studies suggest that the cell that inhibits AIDS virus replication in PBL of infected individuals is a CTL.
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- Brodsky F. M., Parham P., Barnstable C. J., Crumpton M. J., Bodmer W. F. Monoclonal antibodies for analysis of the HLA system. Immunol Rev. 1979;47:3–61. doi: 10.1111/j.1600-065x.1979.tb00288.x. [DOI] [PubMed] [Google Scholar]
- Chakrabarti L., Guyader M., Alizon M., Daniel M. D., Desrosiers R. C., Tiollais P., Sonigo P. Sequence of simian immunodeficiency virus from macaque and its relationship to other human and simian retroviruses. Nature. 1987 Aug 6;328(6130):543–547. doi: 10.1038/328543a0. [DOI] [PubMed] [Google Scholar]
- Chalifoux L. V., Ringler D. J., King N. W., Sehgal P. K., Desrosiers R. C., Daniel M. D., Letvin N. L. Lymphadenopathy in macaques experimentally infected with the simian immunodeficiency virus (SIV). Am J Pathol. 1987 Jul;128(1):104–110. [PMC free article] [PubMed] [Google Scholar]
- Franchini G., Gurgo C., Guo H. G., Gallo R. C., Collalti E., Fargnoli K. A., Hall L. F., Wong-Staal F., Reitz M. S., Jr Sequence of simian immunodeficiency virus and its relationship to the human immunodeficiency viruses. Nature. 1987 Aug 6;328(6130):539–543. doi: 10.1038/328539a0. [DOI] [PubMed] [Google Scholar]
- Kannagi M., Chalifoux L. V., Lord C. I., Letvin N. L. Suppression of simian immunodeficiency virus replication in vitro by CD8+ lymphocytes. J Immunol. 1988 Apr 1;140(7):2237–2242. [PubMed] [Google Scholar]
- Kannagi M., Kiyotaki M., Desrosiers R. C., Reimann K. A., King N. W., Waldron L. M., Letvin N. L. Humoral immune responses to T cell tropic retrovirus simian T lymphotropic virus type III in monkeys with experimentally induced acquired immune deficiency-like syndrome. J Clin Invest. 1986 Nov;78(5):1229–1236. doi: 10.1172/JCI112706. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Kannagi M., Yetz J. M., Letvin N. L. In vitro growth characteristics of simian T-lymphotropic virus type III. Proc Natl Acad Sci U S A. 1985 Oct;82(20):7053–7057. doi: 10.1073/pnas.82.20.7053. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Letvin N. L., Daniel M. D., Sehgal P. K., Desrosiers R. C., Hunt R. D., Waldron L. M., MacKey J. J., Schmidt D. K., Chalifoux L. V., King N. W. Induction of AIDS-like disease in macaque monkeys with T-cell tropic retrovirus STLV-III. Science. 1985 Oct 4;230(4721):71–73. doi: 10.1126/science.2412295. [DOI] [PubMed] [Google Scholar]
- Meuer S. C., Schlossman S. F., Reinherz E. L. Clonal analysis of human cytotoxic T lymphocytes: T4+ and T8+ effector T cells recognize products of different major histocompatibility complex regions. Proc Natl Acad Sci U S A. 1982 Jul;79(14):4395–4399. doi: 10.1073/pnas.79.14.4395. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Morimoto C., Letvin N. L., Boyd A. W., Hagan M., Brown H. M., Kornacki M. M., Schlossman S. F. The isolation and characterization of the human helper inducer T cell subset. J Immunol. 1985 Jun;134(6):3762–3769. [PubMed] [Google Scholar]
- Morimoto C., Letvin N. L., Distaso J. A., Aldrich W. R., Schlossman S. F. The isolation and characterization of the human suppressor inducer T cell subset. J Immunol. 1985 Mar;134(3):1508–1515. [PubMed] [Google Scholar]
- Morimoto C., Rudd C. E., Letvin N. L., Schlossman S. F. A novel epitope of the LFA-1 antigen which can distinguish killer effector and suppressor cells in human CD8 cells. Nature. 1987 Dec 3;330(6147):479–482. doi: 10.1038/330479a0. [DOI] [PubMed] [Google Scholar]
- Neefjes J. J., Breur-Vriesendorp B. S., van Seventer G. A., Iványi P., Ploegh H. L. An improved biochemical method for the analysis of HLA-class I antigens. Definition of new HLA-class I subtypes. Hum Immunol. 1986 Jun;16(2):169–181. doi: 10.1016/0198-8859(86)90046-7. [DOI] [PubMed] [Google Scholar]
- Ortaldo J. R., Longo D. L. Human natural lymphocyte effector cells: definition, analysis of activity, and clinical effectiveness. J Natl Cancer Inst. 1988 Sep 7;80(13):999–1010. doi: 10.1093/jnci/80.13.999. [DOI] [PubMed] [Google Scholar]
- Plata F., Autran B., Martins L. P., Wain-Hobson S., Raphaël M., Mayaud C., Denis M., Guillon J. M., Debré P. AIDS virus-specific cytotoxic T lymphocytes in lung disorders. Nature. 1987 Jul 23;328(6128):348–351. doi: 10.1038/328348a0. [DOI] [PubMed] [Google Scholar]
- Rudd C. E., Morimoto C., Wong L. L., Schlossman S. F. The subdivision of the T4 (CD4) subset on the basis of the differential expression of L-C/T200 antigens. J Exp Med. 1987 Dec 1;166(6):1758–1773. doi: 10.1084/jem.166.6.1758. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Sanders M. E., Makgoba M. W., Shaw S. Human naive and memory T cells: reinterpretation of helper-inducer and suppressor-inducer subsets. Immunol Today. 1988 Jul-Aug;9(7-8):195–199. doi: 10.1016/0167-5699(88)91212-1. [DOI] [PubMed] [Google Scholar]
- Springer T. A., Dustin M. L., Kishimoto T. K., Marlin S. D. The lymphocyte function-associated LFA-1, CD2, and LFA-3 molecules: cell adhesion receptors of the immune system. Annu Rev Immunol. 1987;5:223–252. doi: 10.1146/annurev.iy.05.040187.001255. [DOI] [PubMed] [Google Scholar]
- Walker B. D., Chakrabarti S., Moss B., Paradis T. J., Flynn T., Durno A. G., Blumberg R. S., Kaplan J. C., Hirsch M. S., Schooley R. T. HIV-specific cytotoxic T lymphocytes in seropositive individuals. Nature. 1987 Jul 23;328(6128):345–348. doi: 10.1038/328345a0. [DOI] [PubMed] [Google Scholar]
- Walker B. D., Flexner C., Paradis T. J., Fuller T. C., Hirsch M. S., Schooley R. T., Moss B. HIV-1 reverse transcriptase is a target for cytotoxic T lymphocytes in infected individuals. Science. 1988 Apr 1;240(4848):64–66. doi: 10.1126/science.2451288. [DOI] [PubMed] [Google Scholar]
- Walker C. M., Moody D. J., Stites D. P., Levy J. A. CD8+ lymphocytes can control HIV infection in vitro by suppressing virus replication. Science. 1986 Dec 19;234(4783):1563–1566. doi: 10.1126/science.2431484. [DOI] [PubMed] [Google Scholar]
- Watkins D. I., Kannagi M., Stone M. E., Letvin N. L. Major histocompatibility complex class I molecules of nonhuman primates. Eur J Immunol. 1988 Sep;18(9):1425–1432. doi: 10.1002/eji.1830180919. [DOI] [PubMed] [Google Scholar]
- Zinkernagel R. M., Doherty P. C. Restriction of in vitro T cell-mediated cytotoxicity in lymphocytic choriomeningitis within a syngeneic or semiallogeneic system. Nature. 1974 Apr 19;248(5450):701–702. doi: 10.1038/248701a0. [DOI] [PubMed] [Google Scholar]