MODULATION OF BCL-2 PROTEIN BY CD4 CROSS-LINKING - A POSSIBLE MECHANISM FOR LYMPHOCYTE APOPTOSIS IN HUMAN-IMMUNODEFICIENCY-VIRUS INFECTION AND FOR RESCUE OF APOPTOSIS BY INTERLEUKIN-2

We have previously demonstrated that CD4 cross-linking (CD4XL) results in apoptosis of CD4(+) T cells and augmentation of Fas antigen (CD95, APO-1) expression in CD4(+) and CD8(+) T cells. Here we demonstrate t hat CD4XL mediated by both, anti-CD4 monoclonal antibody (MoAb) or hum an immunodeficiency virus (HIV) envelope protein gp120 reduces the exp ression of the proto-oncogene Bcl-2 in CD4(+) T cells, but not in CD8( +) T cells, concurrently with the induction of CD4(+) T cell-apoptosis . Additionally, the Bcl-2(dim) population expressed high levels of Fas antigen. Bax, an antagonist of Bcl-2, was brightly expressed even in the Bcl-2(dim) population. Addition of interleukin (IL)-2 rescued CD4( +) T cells from CD4XL-induced Bcl-2 downmodulation and apoptosis induc tion. These results support the hypothesis that CD4 ligation by HIV-1 envelope protein in vivo in HIV-infected patients selectively reduces Bcl-2 protein in CD4(+) T lymphocytes, thereby facilitating Fas/Fas-li gand triggered apoptosis; furthermore the findings reported expand the rationale for use of IL-2 in HIV disease. (C) 1997 by The American So ciety of Hematology.