PRIMING WITH IFN-GAMMA RESTORES DEFICIENT IL-12 PRODUCTION BY PERIPHERAL-BLOOD MONONUCLEAR-CELLS FROM HIV-SEROPOSITIVE DONORS

Production of IL-12 is deficient in PBMC from HIV-infected individuals . Because of recent studies demonstrating that IFN-gamma priming incre ases the production of IL-12 in normal PBMC, we examined the role of I FN-gamma in the production of IL-12 in PBMC from HIV-seropositive dono rs. In response to Staphylococcus aureus, production of IFN-gamma and IL-12 was reduced in PBMC from HIV-seropositive compared with that fro m HIV-seronegative donors. Priming with IFN-gamma, through increases i n both IL-12 p40 and p35 mRNA levels, caused a significant increase in IL-12 release by PBMC from both HIV-seropositive and HIV-seronegative donors. However, the increase was greater for PBMC from HIV-seroposit ive donors, largely restoring the deficit in IL-12 production seen in unprimed cells, In response to Cryptococcus neoformans, Candida albica ns, and Mycobacterium tuberculosis, three pathogens that frequently ca use opportunistic infections in persons with AIDS, IFN-gamma productio n was also reduced in PBMC from HIV-seropositive compared with seroneg ative donors. When primed with IFN-gamma, PBMC from both HIV-seroposit ive and seronegative donors released substantial and similar quantitie s of IL-12 in response to these organisms. Taken together, these resul ts demonstrate that IFN-gamma can restore the deficit in IL-12 product ion seen in HIV infection.