Role of monocytes on cd4 crosslinking-induced t cells apoptosis in hiv infection

Recent evidence points to an important immunopathogenic role of monocytes in HIV infection as reservoirs of the virus as well as T cell apoptosis-inducers. However, the mechanisms by which monocytes induce T cell apoptosis is ill-defined. We have previously demonstrated that CD4 cross-linking (XL) performed in PBMC resulted in T cell apoptosis induction in an accessory cell-dependent manner. In this study, we examined the role of monocytes in a CD4XL-induced T cell apoptosis system with special reference to interaction of Fas and its ligand (FasL). Here we report that i) depletion of monocytes, but not of B cells or CD8⁺ T cells, abrogates CD4XL-induced T cell apoptosis; conversely, addition of monocytes to purified CD4⁺ T cells leads to apoptosis; il) CD4XL performed in purified CD4⁺ T cells upregulates Fas, but not FasL expression. We favor the hypothesis that CD4XL leads to FasL induction in monocyte and results in bystander T cell apoptosis via a mechanism of FasFasL interaction.