The Journal of Experimental Medicine
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© The Rockefeller University Press, 0022-1007/1997/1/55/ $5.00
The Journal of Experimental Medicine, Volume 185, Number 1, January 6, 1997 55-64


Articles

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

Andrew D. Badley*, David Dockrell*, Margaret Simpson{ddagger}, Ron Schut{ddagger}, 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; {ddagger} 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.


Address correspondence to Dr. Carlos V. Paya, Division of Infectious Diseases, Mayo Clinic, 200 First Street SW, Guggenheim 501, Rochester, MN 55905.

We would like to acknowledge the excellent secretarial assistance of Mr. Douglas Hauschild.

Drs. Badley and Dockrell contributed equally to this work.

1Abbreviation used in this paper: MDM, monocyte derived macrophage.


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