HIV-1 GP160 AS A MODIFIER OF TH1 AND TH2 CYTOKINE RESPONSE - GP160 SUPPRESSES INTERFERON-GAMMA AND INTERLEUKIN-2 PRODUCTION CONCOMITANTLY WITH ENHANCED INTERLEUKIN-4 PRODUCTION IN-VITRO

Disease progression in HIV-1 infection is reported to be associated with a gradual shift in CD4(+) T cell function from a Th type 1 to a Th type 2 of response, but the underlying mechanism remains unclear. In this study, the effect of HIV-1 envelope glycoprotein gp160 on secretion of cytokines IFN-gamma/IL-2 (Thl type) and IL-4 (Th2 type) was analyzed using freshly isolated unfractioned peripheral blood mononuclear cells (PBMC), CD4(+) T cell lines, and PBMC depleted of CD8(+) cells (CD8(-) PBMC) as target cells. Pretreatment of these cells with HIV gp160 significantly reduced PHA-induced secretion of IFN-gamma and IL-2 but augmented IL-4 production. This effect of gp160 was not observed when the target cells consisted of PBMC depleted of either CD4(+) cells (CD4(-) PBMC) or of CD2(+) cells (CD2(-) PBMC). Pretreatment of gp160 with soluble CD4-immunoglobulin chimeric molecules abrogated the observed effects of gp160, suggesting that CD4-gp120 interaction is required for modification of the cytokine secretion profile. Our results suggest that exposure of CD4(+) T cells to HIV-1 envelope proteins may modify the responses evoked by additional stimuli in favor of a Th2-type dominant response. (C) 1994 Academic Press, Inc.