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 increases the production of IL-12 in normal PBMC, we examined the role of IFN-gamma in the production of IL-12 in PBMC from HIV-seropositive donors. In response to Staphylococcus aureus, production of IFN-gamma and IL-12 was reduced in PBMC from HIV-seropositive compared with that from HIV-seronegative donors. Priming with IFN-gamma, through increases in 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-seropositive donors, largely restoring the deficit in IL-12 production seen in unprimed cells. In response to Cryptococcus neoformans, Candida albicans, and Mycobacterium tuberculosis, three pathogens that frequently cause opportunistic infections in persons with AIDS, IFN-gamma production was also reduced in PBMC from HIV-seropositive compared with seronegative donors. When primed with IFN-gamma, PBMC from both HIV-seropositive and seronegative donors released substantial and similar quantities of IL-12 in response to these organisms. Taken together, these results demonstrate that IFN-gamma can restore the deficit in IL-12 production seen in HIV infection.
Harrison
T S
TS
Evans Memorial Department of Clinical Research, Boston University Medical Center Hospital, MA 02118, USA.
Levitz
S M
SM
D000163:Acquired Immunodeficiency Syndrome / Q000276:immunology / Q000378:metabolism; D006679:HIV Seropositivity / Q000276:immunology* / Q000378:metabolism; D006801:Humans; D007114:Immunization; D007371:Interferon-gamma / Q000096:biosynthesis / Q000276:immunology* / Q000494:pharmacology*; D018664:Interleukin-12 / Q000096:biosynthesis* / Q000172:deficiency*; D007963:Leukocytes, Mononuclear / Q000187:drug effects* / Q000378:metabolism*
D018664:Interleukin-12; D007371:Interferon-gamma