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 HlV-infected, but not from uninfected control individuals. Tills 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, Fast and tumor necrosis factor (TNF), mediate this macrophage-induced apoptosis of CD4(+) T cells. These results support a role for macrophage-associated Fast and TNF ill the selective depletion of CD4(+) T cells in HIV-infected individuals.