IL-15 ENHANCES IMMUNE FUNCTIONS DURING HIV-INFECTION

IL-15, a new cytokine primarily produced by macrophages, has been show n to exhibit several functional properties shared with IL-2. Treatment of PBMC from HIV-infected patients with IL-15 resulted in an increase in NK cell cytotoxicity to levels similar to those of untreated PBMC from healthy donors, This effect is independent of several well-charac terized regulatory cytokines, as it is not prevented by Abs that neutr alize IFNs, TNF-alpha, IL-2, or IL-12. Enhanced cytotoxicity was accom panied by a significant increase in expression of cytotoxic granules, IL-15 enhanced the proliferative ability in both controls and HIV-sero positive in response to mitogen and recall Ags, Although the addition of IL-15 has a preventive effect on the appearance of spontaneous cell death, this effect was not seen during mitogen-induced apoptosis, The production of IL-15 by PBMC from patients in response to Staphylococc us aureus Cowan strain 1 appeared heterogeneous and was not negatively regulated by cytokines that inhibited IL-12 production, No correlatio n was found between in vitro HIV infection and IL-15 production, as vi ral infection had no effect on the ability of monocytes to produce IL- 15 in response to S. aureus, Interestingly IL-15 restored the deficien t production of IL-12 by PBMC from HIV+ people and had no major effect on modulating viral expression in latently infected cell lines or PBM C from naturally infected people, Taken together, these results sugges t a potent immunoregulatory role of IL-15 during HIV infection.