PRIMING OF HUMAN CD4(-SPECIFIC T-CELLS TO UNDERGO APOPTOSIS BY HIV-INFECTED MONOCYTES - A 2-STEP MECHANISM INVOLVING THE GP120 MOLECULE() ANTIGEN)

The study of the pathology of HIV-1 infection in chimpanzees supports the idea of the crucial role of HIV-infected monocytes in the pathogen esis of AIDS, although viral mechanisms that lead to T cell dysfunctio n and deletion during HIV infection are still unclear. We show here th at HIV-1-infected antigen-presenting monocytes (APCs) are able to prim e in vitro non-HIV-infected antigen-specific CD4(+) T cell lines or pe ripheral blood CD4(+) T cells to undergo apoptosis after antigen-speci fic restimulation. The priming of T cells for apoptosis occurs in the absence of HIV replication in the T cells. Priming for apoptosis requi red two concomitant signals present on the same APC, an antigenic stim ulus and a second signal provided by the HIV gp120 protein as demonstr ated by the use as APCs of EBV-LCLs infected with different recombinan t deleted proviruses or transfected with different HIV proteins. These results provide a mechanism for the priming for apoptosis of T cells in HIV-infected patients, implicating a role for HIV-infected APCs in the induction of T cell dysfunction and depletion in AIDS.