J. Exp. Med.
© The Rockefeller University Press
0022-1007/97/01/55/10 $2.00
Volume 185 January 1997 55-64

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

By Andrew D. Badley,^* David Dockrell,^* Margaret Simpson, Ron Schut, David H. Lynch,^§ Paul Leibson, and Carlos V. Paya^¶*

From the ^* Division of Infectious Diseases, ^¶ Division of Experimental Pathology, and  Department of Immunology, Mayo Clinic, Rochester, Minnesota 55901;  Division of Infectious Diseases, Hennepin County Medical Center, Minneapolis, Minnesota 55404; and ^§ Immunex Corporation, Seattle, Washington 98101

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.

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