It has been previously demonstrated that the occupancy of CD4 molecules by the HIV-1 envelope glycoprotein gp120 results in marked inhibition of T cell receptor-CD3 complex (TCR/CD3) activation-induced IL-2 secretion. To elucidate the mechanism of inhibitory effects of gp160 on T cell signaling, we have investigated the intracellular biochemical events and biological output in response to anti-CD3 mAb activation of purified peripheral blood CD4+ T cells from healthy donors with and without prior exposure to HIV-41 gp160. Pretreatment with gp160 resulted in marked inhibition of tyrosine phosphorylation of p59(fyn) PLC-γ1, ras activation, and TNF-α secretion in anti-CD3 mAb activated CD4+ T cells, and a subset of CD4+ cells underwent activation-induced cell death. The data presented here provide insight into the mechanism by which the interaction of HIV-1 envelope glycoproteins with CD4 molecules may alter TCP/CD3-activation-induced signal transduction resulting in anergy and apoptosis with consequent functional deficiency of CD4+ T cells.
ASJC Scopus subject areas
- Immunology and Allergy
- Pathology and Forensic Medicine