Evidence of a role for TNF-alpha in cytolysis by CD4+, class II MHC-restricted cytotoxic T cells.

Variants of the tumour necrosis factor (TNF)-sensitive cell lines BALB/c 3T3 and WEHI-164/13 were generated by selection in high concentrations of recombinant TNF-alpha. The selected cells were highly resistant to cytolysis by both TNF-alpha and TNF-beta (lymphotoxin); however, there was no significant difference in sensitivity to killing by class I major histocompatibility complex (MHC)-restricted cytotoxic T lymphocytes (CTL). Resistance to TNF-mediated lysis was, however, accompanied by increased resistance to cytolysis by CD4+ class II-restricted CTL. Furthermore, cytolysis of WEHI-164/13 cells by CD4+ was completely inhibited by anti-TNF antiserum. These data strongly suggest a role for TNF in killing by CD4+ class II MHC-restricted CTL but not in class I MHC-restricted killing.