Macrophage-dependent Apoptosis of CD4⁺ T Lymphocytes from HIV-infected Individuals Is Mediated by FasL and Tumor Necrosis Factor

Apoptosis of bystander uninfected CD4⁺ T lymphocytes by neighboring HIV-infected cells is observed in cell culture and in lymphoid tissue of HIV-infected individuals. This study addresses whether antigen-presenting cells such as human macrophages mediate apoptosis of CD4⁺ T cells from HIV-infected individuals. Uninfected human macrophages, and to a larger degree, HIV-infected macrophages mediate apoptosis of T cells from HIV-infected, but not from uninfected control individuals. This macrophage-dependent killing targets CD4⁺, but not CD8⁺ T lymphocytes from HIV-infected individuals, and direct contact between macrophages and lymphocytes is required. Additional analyses indicated that the apoptosis-inducing ligands, FasL and tumor necrosis factor (TNF), mediate this macrophage-induced apoptosis of CD4⁺ T cells. These results support a role for macrophage-associated FasL and TNF in the selective depletion of CD4⁺ T cells in HIV-infected individuals.