AEGiS-11IAC: Dual activity of a human CTL clones: cytotoxic activity and control of virus replication.

11th International AIDS Conference

Vancouver, British Columbia — July 7-12, 1996

Dual activity of a human CTL clones: cytotoxic activity and control of virus replication.

Int Conf AIDS 1996 Jul 7-12; 11:210 (abstract no. Th.A.103)
Fevrier M, Buseyne F, Schwartz O, Stevanovic S, Rammensee H-G, Riviere Y; UVIC, Institut Pasteur, Paris, France. Fax: 33140613012.

OBJECTIVE: During HIV infection, a vigorous CTL response has been described, directed against most structural and regulatory viral proteins. Polyclonal CD8+ populations, with or without CTL activity, were able to inhibit HIV replication in vitro, implicating soluble inhibitors. Recent papers suggest that IL 16, RANTES, MIP-1a and MIP-1b could exert such a control of viral replication. The aim of our work was to explore if, at a clonal level, the same cell could exert cytolytic activity and control of viral replication, and what is the relative contribution of each activity.

METHODS: We characterized 2 CTL clones, one recognized aa 73-82 from p27nef in an HLA-All restricted manner (clone P1) and one specific for aa 308-316 from p24gag, restricted by an HLA-C molecule (clone 141). Clones were cocultured with HIV-1-infected CD4+ T cells, and viral replication was followed by measuring RT activity in the supernatants. Two experimental conditions were tested: cell contacts were permitted or not (culture in transwell vessels).

RESULTS: When cell contacts were permitted, the two clones controlled HIV replication in autologous CD4+ and in heterologous CD4+ T cells infected in vitro with HIV-1LAI. Involvement of diffusible factors was demonstrated for clone 141 by culturing infected CD4+ T cells and CD8+ CTL in separate chambers. Similar results were obtained using a different approach with the P1 clone: CD4+ T cells were infected with an HIV isolate which did not express the epitope recognized by P1. Control of viral replication was always better when cell contacts and cytotoxic activity were allowed. Furthermore production of soluble inhibitory factors was not constitutive but depended on TCR activation.

CONCLUSION: We demonstrated, at a clonal level, that a CD8+ T cell can mediate both specific lysis and nonlytic suppression of HIV replication. Both activities are required to obtain optimal control of viral replication.

Keywords: AEGIS, Virus Replication, Clone Cells, HIV-1, Antigens, CD4, Antigens, CD8, T-Lymphocytes, Cytotoxic, HIV Infections, CD4-Positive T-Lymphocytes, CD8-Positive T-Lymphocytes, T-Lymphocytes, Receptors, Antigen, T-Cell, RANTES, HLA-C Antigens, Epitopes, HLA Antigens, Human, In Vitro, virology, ICA11

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ThA103