AEGiS-11IAC: Identification of multiple activities produced by CD8+ T cells that suppress HIV-replication.

11th International AIDS Conference

Vancouver, British Columbia — July 7-12, 1996

Identification of multiple activities produced by CD8+ T cells that suppress HIV-replication.

Int Conf AIDS 1996 Jul 7-12; 11:210 (abstract no. Th.A.100)
Weissman D, Rubbert A, Barker TD, Daucher JA, Pettrone K, Fauci AS; National Institutes of Health, Bethesda, MD, USA. Fax: 301-402-4122.

OBJECTIVE: To identify factors produced by CD8+ T cells that suppress HIV replication using an in vitro system that models the paracortical regions of lymphoid tissue.

METHODS: The culture system used dendritic cells (DC) to activate CD4+ T cells in the absence of added mitogen. Two different systems were employed; the first, an acute infection system, used DC and CD4+ T cells from uninfected people, and the DC were pulsed with HIV, primary or lab isolates, at multiplicities of infection ranging from 0.1 to 0.0001; the second, the endogenous infection system, used DC and CD4+ T cells from HIV-infected individuals. CD8+ T cells were added at the initiation of the culture.

RESULTS: Two sets of activities were identified. One activity inhibited in the endogenous system and was expressed in CD8+ T cells from both HIV-infected and uninfected individuals. The second activity suppressed in the acute system and was only produced by CD8+ T cells from HIV-infected individuals; in fact, CD8+ T cells from uninfected people often enhanced viral replication. These activities could be further differentiated in that the activity in the endogenous system was lost with HIV disease progression while the activity in the acute system was present even in late stage patients (CD4 counts less than 100/ul). Pretreatment of CD8+ T cells with gamma irradiation abrogated suppression in the acute infection system, but had no effect in the endogenous system. Transwell experiments indicate that both activities are mediated by soluble factors The addition of MIP-1 alpha, MIP-1beta, Rantes, or IL-16 to either the acute or endogenous DC systems did not induce suppression of viral replication. The addition of neutralizing antibodies against MIP-1 alpha, MIP-1beta, and Rantes to cocultures of DC, CD4+, and CD8+ T cells did not block the ability of the CD8+ T cells to inhibit viral replication.

CONCLUSIONS: Two activities that differ in their elaboration by CD8+ T cells from HIV-infected versus uninfected individuals, evolution with disease stage, and sensitivity to pretreatment of CD8+ T cells with gamma irradiation have been identified. These results indicate that CD8+ T cell modulation of HIV replication in CD4+ T cells may be a multi-factorial phenomenon involving multiple inhibitory and enhancing factors.

Keywords: AEGIS, HIV, Antigens, CD8, Virus Replication, T-Lymphocytes, HIV Infections, Macrophage Inflammatory Protein-1, RANTES, CD8-Positive T-Lymphocytes, CD4-Positive T-Lymphocytes, Antigens, CD4, Dendritic Cells, HIV Core Protein p24, HIV Long Terminal Repeat, T-Lymphocytes, Suppressor-Effector, In Vitro, Human, virology, genetics, ICA11

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