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 wi th 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 t his study, the effect of HIV-1 envelope glycoprotein gp160 on secretio n of cytokines IFN-gamma/IL-2 (Thl type) and IL-4 (Th2 type) was analy zed using freshly isolated unfractioned peripheral blood mononuclear c ells (PBMC), CD4(+) T cell lines, and PBMC depleted of CD8(+) cells (C D8(-) PBMC) as target cells. Pretreatment of these cells with HIV gp16 0 significantly reduced PHA-induced secretion of IFN-gamma and IL-2 bu t augmented IL-4 production. This effect of gp160 was not observed whe n the target cells consisted of PBMC depleted of either CD4(+) cells ( CD4(-) PBMC) or of CD2(+) cells (CD2(-) PBMC). Pretreatment of gp160 w ith soluble CD4-immunoglobulin chimeric molecules abrogated the observ ed effects of gp160, suggesting that CD4-gp120 interaction is required for modification of the cytokine secretion profile. Our results sugge st that exposure of CD4(+) T cells to HIV-1 envelope proteins may modi fy the responses evoked by additional stimuli in favor of a Th2-type d ominant response. (C) 1994 Academic Press, Inc.