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.
Badley
A D
AD
Division of Infectious Diseases, Mayo Clinic, Rochester, Minnesota 55901, USA.
Dockrell
D
D
Simpson
M
M
Schut
R
R
Lynch
D H
DH
Leibson
P
P
Paya
C V
CV
D000911:Antibodies, Monoclonal; D000954:Antigens, Surface / Q000502:physiology; D017209:Apoptosis; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000502:physiology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D002478:Cells, Cultured; D018920:Coculture Techniques; D053222:Fas Ligand Protein; D005434:Flow Cytometry; D015658:HIV Infections / Q000276:immunology*; D018023:HIV Seronegativity; D006679:HIV Seropositivity / Q000276:immunology; D006801:Humans; D008221:Lymphoid Tissue / Q000276:immunology; D008264:Macrophages / Q000276:immunology*; D008562:Membrane Glycoproteins / Q000502:physiology*; D011993:Recombinant Fusion Proteins / Q000276:immunology; D014409:Tumor Necrosis Factor-alpha / Q000502:physiology*
D000911:Antibodies, Monoclonal; D000954:Antigens, Surface; C505661:FASLG protein, human; D053222:Fas Ligand Protein; D008562:Membrane Glycoproteins; D011993:Recombinant Fusion Proteins; D014409:Tumor Necrosis Factor-alpha