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.