AEGiS-11IAC: CD8+ T cell-mediated suppression of HIV replication: relevance of known chemokines and other cytokines.

11th International AIDS Conference

Vancouver, British Columbia — July 7-12, 1996

CD8+ T cell-mediated suppression of HIV replication: relevance of known chemokines and other cytokines.

Int Conf AIDS 1996 Jul 7-12; 11:226 (abstract no. Tu.A.390)
Mackewicz CE, Barker E, Orque R, Levy JA; Cancer Research Institute, University of California-San Francisco, San Francisco, CA, USA. Fax: (415) 476-8365.

OBJECTIVE: To determine if the CD8+ cell antiviral factor (CAF) produced by CD8+ cells from HIV-infected individuals is a known cytokine.

METHODS: Levels of the chemokines, RANTES, MIP-1alpha, MIP-1beta, and MCP-1 were measured by ELISA in CD8+ cell culture fluids that either suppressed (CAF-positive) or had no effect (CAF-negative) on HIV-1 replication in acutely infected CD4+ cells. Recombinant human IL-13, IL-16, LIF, and the chemokines, RANTES, MIP-1alpha, MIP-beta, MCP-1, MCP-3, IP-10, lymphotactin, Gro-alpha, and Gro-beta at a range of concentrations were tested for inhibitory activity against HIV replication in naturally and acutely infected CD4+ cells. Finally, CAF-positive culture fluids were pretreated with a mixture of neutralizing antibodies specific for RANTES, MIP-1alpha, and MIP-1beta, prior to assessing inhibitory effects on HIV replication.

RESULTS: CD8+ T cells from HIV-infected individuals produced levels of certain chemokines (e.g., that RANTES, MIP-1alpha, MIP-1beta) maximally reach about 10 ng/ml early after activation and gradually drop over a two week period in culture. Both CAF-positive and CAF-negative fluids had levels of RANTES, MIP-1alpha, and MIP-1beta ranging from 0.1 to 9.5 ng/ml. The level of chemokines present in CD8+ cell supernatants did not correlate with the level of their anti-HIV activity. Only recombinant human RANTES, MIP-1beta, MCP-3, and lymphotactin suppressed HIV replication (by greater than or equal to50%) but at higher concentrations (greater than or equal to100 ng/ml) than produced by CD8+ T cells. No significant antiviral activity was noted with IL-13, IL-6, LIF and the other chemokines. Neutralizing antibodies to RANTES, MIP-1alpha, and MIP-1beta, in combination, had no effect on the ability of CD8+ cell culture fluids to suppress HIV replication.

CONCLUSIONS: Some chemokines have anti-HIV activity in vitro at much higher concentrations than found in CD8+ cell culture fluids. The anti-HIV activity detected in CD8+ cell culture fluids appears to be due to a cellular factor(s) (CAF) distinct from known chemokines and other cytokines.

Keywords: AEGIS, Chemokines, Virus Replication, Antigens, CD8, Macrophage Inflammatory Protein-1, RANTES, HIV-1, T-Lymphocytes, CD8-Positive T-Lymphocytes, Monocyte Chemoattractant Proteins, Monocyte Chemoattractant Protein-1, Anti-HIV Agents, CD4-Positive T-Lymphocytes, monocyte chemoattractant protein-3, Human, In Vitro, virology, ICA11

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TuA390