THE CELL-SURFACE MARKER PHENOTYPE OF MACROPHAGES FROM HIV-1-INFECTED SUBJECTS REFLECTS AN IL-10-ENRICHED AND IFN-GAMMA-DEPRIVED DONOR ENVIRONMENT

T cells depend on costimulation by accessory cells for an immune respo nse, Costimulatory macrophage activity involves the expression of B7 m olecules whose expression is upregulated by interferon-gamma (IFN-gamm a) and downregulated by interleukin-10 (IL-10). The expression of low- affinity Fc gamma IIIR (CD16), in contrast, is upregulated in the pres ence of IL-10 and downregulated in the presence of IFN-gamma, In human immunodeficiency virus-1 (HIV-1) infection, the balance between IFN-g amma and IL-10 expression shifts toward IL-10 predominance, Herein, we compare B7 and CD16 macrophage phenotypes from healthy and from HIV-1 -infected patients, Patient macrophages express B7 molecules in lower density than macrophages from healthy donors and are resistant to the upregulation of costimulatory molecule expression, B7 expression can b e normalized in patient macrophages by treating them with anti IL-10 m onoclonal antibodies (mAb) and IFN-gamma together but not by treatment with either anti-IL-10 mAb or IFN-gamma alone, This finding suggests an excess of IL-10 in HIV-1 infection and an IFN-gamma deficiency, con sistent with previous cytokine assessments in HIV-1-infected subjects, The upregulation of CD16 expression was readily induced in patient ma crophages by treatment with IL-10 and was inhibited by treatment with IFN-gamma. CD16 expression identifies the subset of cytotoxic macropha ges that has been shown to destroy CD4 T cells, which they target thro ugh CD4-reactive immune-complexed HIV-1 envelope molecules.