Fas ligand-mediated depletion of CD4 and CD8 lymphocytesby monomeric HIV-1-gp120

Abstract

In order to determine in what condition and by what mechanism gp 120 can deplete not only CD4 but also CD8 T cells, an in vitro system was established in which peripheral blood lymphocytes from healthy donors were treated with recombinant gp 120. We found that gp 120 can deplete both CD4 and CD8 T cells when they have recently been activated and are exposed to IL-2-deficient conditions. Bioassay of the Fas ligand (FasL) demonstrated augmented expression and release of soluble FasL by CD4 T cells in the supernatant of this culture. The administration of anti-FasL mAb and anti-Fas mAb, both of which exhibit neutralizing activity, completely abolished the depletion of these two T cell populations in culture. Based on these findings, we concluded that FasL depletes Fas antigen expressing CD4 and CD8 T cells by programmed cell death.

Retroviral membrane display of apoptotic effector molecules

“…Depletion of these cells is a contributing factor in the etiology of AIDS. Although the mechanism by which this occurs is still under extensive investigation, some reports indicate that it is the envelope protein of HIV-1, gp120, perhaps in conjunction with the viral-encoded protein Tat, that facilitates the activation of the Fas death pathway by inducing the expression of FasL (18,23,26). Our report opens another possibility, namely that the virus might mediate the cell-death signal by inheriting FasL protein after budding from a highly activated cell.…”

“…The first form is mediated by the full-length transmembrane FasL (16)(17)(18). The second is mediated by a soluble FasL (sFasL) proteolytically cleaved by metalloproteinase digestion from the transmembrane form and released into the culture medium.…”

Rubella virus-induced cytopathic effect in vitro is caused by apoptosis.

“…Examples include gp120 of human immunodeficiency virus, G protein of rabies virus and E2 protein of Sindbis virus (Uchiyama et al, 1997 ;Thoulouze et al, 1997 ;Ubol et al, 1994 ;Joe et al, 1998). Surprisingly, the RV structural proteins, C, E2 and E1, were not able to induce apoptosis when expressed in Vero cells.…”

Partial Activation and Induction of Apoptosis in CD4+and CD8+T Lymphocytes by Conformationally Authentic Noninfectious Human Immunodeficiency Virus Type 1

“…2A). Because rgp120 has been reported to induce apoptosis (10,56,75), we also examined the effect of rgp120 on freshly isolated PBMC. At very high concentrations (1,000 to 10,000 ng/ml), rgp120 stimulated the PBMC to proliferate and undergo apoptosis (data not shown) and deplete CD4 ϩ T cells ( Fig.…”