IN-VITRO IMMUNOLOGICAL AND VIROLOGICAL EFFECTS OF INTERLEUKIN-15 ON PERIPHERAL-BLOOD MONONUCLEAR-CELLS FROM NORMAL DONORS AND HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1-INFECTED PATIENTS

Interleukin 15 (IL-15) is a cytokine that shares receptor subunits and functional activity, such as T-cell and B-cell stimulation, with IL-2 . The effect of IL-2 on immune function and human immunodeficiency vir us (HIV) viral load in HIV-infected patients is being actively studied . Thus, we examined how IL-15 compares with IL-2 in several in vitro i mmunologic and virologic assays in order to explore whether a rational e exists for pursuing initial clinical therapeutic trials With IL-15. The effects of IL-15 on induction of lymphokine-activated killer (Wt) cells, gamma interferon (IFN-gamma) production from HN-positive periph eral blood mononuclear cells (PBMCs), and HIV production from PBMCs we re studied. Induction of Wt cells by IL-15 was found in eight of eight HIV positive donors. Incubation of PBMCs from some donors with IL-15 (1, 10, 50, and 100 ng/ml) induced production of IFN-gamma. The effect of IL-15 was compared with that of IL-2 on HIV replication in PBMCs f rom five HIV-positive patients and four HIV-negative donors whose PBMC s were infected in vitro with HIV. Levels of HIV p24 antigen were mode rately lower in the presence of 10 ng of IL-15 per mi than with 10 ng of IL-2 per mi, but they were similar for 100 and 500 ng of each cytok ine per mi. In summary, IL-15 can induce LAK cell activity in HIV-sero positive patients and can stimulate IFN-gamma production from PBMCs of some donors. IL 15 stimulates levels of HIV production from PBMCs whi ch are similar to or moderately lower than those obtained with IL-2, d epending on cytokine concentration.