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 (Th1 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.
Hu
R
R
Department of Pediatrics, North Shore University Hospital-Cornell University Medical College, Manhasset, New York, New York 11030.
Oyaizu
N
N
Kalyanaraman
V S
VS
Pahwa
S
S
D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D016207:Cytokines / Q000096:biosynthesis* / Q000378:metabolism; D015686:Gene Products, env / Q000502:physiology*; D019302:HIV Envelope Protein gp160; D006801:Humans; D007372:Interferons / Q000096:biosynthesis; D007376:Interleukin-2 / Q000096:biosynthesis; D015847:Interleukin-4 / Q000096:biosynthesis; D011498:Protein Precursors / Q000502:physiology*; D018417:Th1 Cells / Q000378:metabolism*; D018418:Th2 Cells / Q000378:metabolism*
D016207:Cytokines; D015686:Gene Products, env; D019302:HIV Envelope Protein gp160; D007376:Interleukin-2; D011498:Protein Precursors; D015847:Interleukin-4; D007372:Interferons