CD4+ T cells require adhesion via LFA-1/ICAM-1 to induce target apoptosis in TNF-independent pathway.
An antigen-specific CD4+ T cell clone, OK2.21, and a hybridoma clone, A3.4C6, induced cytolysis and DNA fragmentation of appropriate targets in the presence of an anti-CD3 monoclonal antibody (Mab). In a double chamber system, OK2.21 killed TNF-sensitive targets that were separated from the T cells by a porous membrane. The killing was completely inhibited by anti-TNF antibody. On the other hand, neither OK2.21 nor A3.4C6 killed a TNF-insensitive target, A20.2J, that was separated from the T cells. Furthermore, the cytotoxicity and DNA fragmentation of A20.2J by anti-CD3 Mab-activated T cells were inhibited by both anti-LFA-1 and anti-ICAM-1 Mab. These results suggest that TNF is the only soluble cytolytic factor involved in CD4+ T cell-mediated cytotoxicity, and that TNF-independent apoptosis occurs through cell-to-cell contact via a LFA-1/ICAM-1 system.
Okazaki
T
T
Department of Internal Medicine, Faculty of Medicine, Kyoto University, Japan.
Ozaki
S
S
Nakao
K
K
D000818:Animals; D017209:Apoptosis; D017252:CD3 Complex / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology*; D002448:Cell Adhesion; D015815:Cell Adhesion Molecules / Q000502:physiology; D002999:Clone Cells; D003602:Cytotoxicity, Immunologic; D004249:DNA Damage; D007111:Immunity, Cellular; D018799:Intercellular Adhesion Molecule-1; D016169:Lymphocyte Function-Associated Antigen-1 / Q000502:physiology; D051379:Mice; D008807:Mice, Inbred BALB C; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*
D017252:CD3 Complex; D015815:Cell Adhesion Molecules; D016169:Lymphocyte Function-Associated Antigen-1; D014409:Tumor Necrosis Factor-alpha; D018799:Intercellular Adhesion Molecule-1