Cytotoxic cell proteinase gene expression and cytolytic activity by anti‐CD3‐activated cytotoxic T lymphocytes is sensitive to cyclosporin A but is not dependent on interleukin‐2 synthesis

We have examined the role of interleukin (IL) 2 in the expression of cytotoxic cell proteinases (CCP) 1 and 2, as well as in the induction of major histocompatibility complex (MHC)‐unrestricted cytotoxic activity in murine T cell cultures following stimulation with anti‐ CD3 monoclonal antibody. A dramatic reduction in CCP‐1 and CCP‐2 gene expression and near absence of cytolytic activity was shown to occur in these cultures when the expression of IL‐2 was inhibited by 10 −6 M cyclosporin A (CsA). The inhibitory effect of CsA could not be eliminated by the addition to culture of recombinant IL‐2 at concentrations typically present in anti‐ GD3‐stimulated T cell culture supernatants. Furthermore, when endogenous IL‐2 (45‐60 U/ml) present in anti‐CD3‐stimulated T cell cultures was neutralized with anti‐mouse IL‐2 antibody there was no effect on CCP‐1 and CCP‐2 mRNA expression and only a slight decrease in cytolytic activity. The expression of CCP‐1 and CCP‐2 gene products and the induction of MHC‐unrestricted cytotoxic activitv in anti‐CD3‐stimulated T cell cultures therefore occur independently of IL‐2 synthesis but are regulated by a CsA‐sensitive mechanism.