Priming for high interferon-gamma production induced by interleukin-12 in both CD4+ and CD8+ T cell clones from HIV-infected patients.

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Abstract

HIV-infected patients are defective in their ability to produce interleukin (IL)-12 in vitro in response to pathogenic bacteria and parasites. IL-12 enhances the patient's depressed natural killer cell cytotoxic activity, peripheral blood lymphocyte production of interferon-gamma (IFN-gamma), and proliferative T cell response in vitro to recall antigens, HIV antigens, alloantigens, and mitogens. However, these effects represent short-lived responses and imply the need for chronic IL-12 therapeutic administration in the clinical setting. To identify any long-term effects of IL-12 on T cell differentiation toward Th1 cells, peripheral blood T cells from 10 HIV-infected patients at different stages of disease were cloned by limiting dilution in the presence or absence of IL-12 and tested for cytokine production in response to stimulation with anti-CD3 antibodies and phorbol diesters IL-12 present during the first 2 wk of clonal expansion determined a stable severalfold enhancement on the ability of both CD4+ and CD8+ clones to produce IFN-gamma. Because priming for high IFN-gamma production is probably the most important mechanism by which IL-12 induces generation of efficient T helper type 1 (Th1) cells, these results suggest the possibility that IL-12 treatment in vivo of HIV-infected patients may stimulate a protective Th1 response against opportunistic pathogens and possibly HIV itself.

Authors

C Paganin, I Frank, G Trinchieri