Interleukin-12 enhances antigen-specific proliferation of peripheral blood mononuclear cells from HIV-positive and negative donors in response to Mycobacterium avium.

OBJECTIVE: To determine if the addition of recombinant (r) human interleukin (IL)-12 enhances in vitro proliferative responses to Mycobacterium avium of peripheral blood mononuclear cells (PBMC) from HIV-positive donors with CD4 cell counts < 100 x 10(6)/l.

DESIGN AND METHODS: PBMC proliferative responses to virulent and avirulent serovars of M. avium in the presence and absence of exogenously added IL-12 were determined in 24 HIV-positive and 11 HIV-negative donors by 3H-thymidine uptake assay. Changes in CD4 and CD8 cell populations after IL-12 treatment and M. avium stimulation were analyzed by FACS.

RESULTS: IL-12 significantly enhanced proliferation of PBMC to both virulent and avirulent M. avium from all 24 HIV-positive donors (P = 0.0001) although the magnitude varied for each donor. In contrast, addition of IL-12 to PBMC from HIV-negative donors only increased the proliferative responses to the virulent M. avium serovar 4 (P = 0.0044). PBMC from HIV-positive donors in the presence of IL-12 responded better to the avirulent serovar of M. avium than the virulent serovar 4. Proliferative responses of HIV-positive donors to M. avium alone, however, were significantly less (P = 0.0013) than that of HIV-negative donors. Increased proliferative responses of HIV-positive donors were independent of CD4 counts. No significant changes in the ratio of CD4+ to CD8+ T cells occurred in either HIV-positive or negative donors under any culture conditions.

CONCLUSION: In vitro proliferative responses of PBMC from HIV-positive donors to M. avium were significantly enhanced by the addition of human rIL-12, which was not dependent on their CD4 cell counts. The use of IL-12 as an enhancer of cell-mediated immunity in AIDS patients against M. avium infections deserves further study.