Immunoregulatory cytokine changes result from HIV infection, with decreased type 1 cytokines that enhance cellular immunity (CI) and increased type 2 cytokines that inhibit CI. IL-12 and IL-10 increase and decrease CI, respectively, and are produced by antigen-presenting cells (APC) that are monocytes (MC) and dendritic cells (DC), important targets of HIV infection. MC from HIV+ patients produced reduced levels of IL-12 and increased levels of IL-10, as did MC infected in vitro with HIV. In contrast, DC appeared to be resistant to HIV-induced cytokine changes. Therapeutic trials of pediatric AIDS patients with highly active anti-retroviral therapy (HAART) indicated that patients who presented with reduced viral loads and increased CD4 counts did not exhibit normalized IL-12 production, even after 2-3 years of HAART. This finding suggests that multi-drug therapy-induced changes in CD4 count and viral load is not reflected in improved immune function. In vitro production of IL-12 by MC of HIV+ patients was restored by the synergistic effects of IFN-g and CD40 ligand. MC from uninfected newborns of HIV-infected mothers did not produce IL-12, in contrast to the MC of newborns of HIV uninfected mothers that did produce IL-12. The leukocytes of FVB/N mice into which the entire HIV-1 genome had been transfected (HIV-Tg) were studied for expression of HIV. APC stimulating agents such as LPS or M. avium infection upregulated HIV expression/production, but T cell stimuli such as anti-CD-3 did not. However, P. chalaudi, which induces malaria in mice and stimulates T lymphocytes, was able to stimulate HIV expression/production in APC but not in T cells via T cell activated IFN-g production that activated HIV in the APC.
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