Inhibition of Cytotoxic

Transforming growth factor 0 (TGF-0),' although first defined for its ability to induce nonneoplastic cells to express a transformed phenotype, has now been shown to exert multiple actions on both normal andtransformed cells (1). Recent studies have also defined a variety of immunoregulatory properties of TGF-0, including inhibition of T and B cell proliferation, IL-2-R induction, IL-1-induced thymocyte proliferation, cytokine production, including IFN--y and TNF-a, natural killer cell activity, and class 11 antigen expression (2-6). Themechanism(s) through which TGF-0 exerts these immunoregulatory effects is at present not known. TNF-a (also referred to as cachectin) has also been shown to express multifunctional immunomodulatory activities besides its direct cytotoxic/cytostatic effects on transformed cells (7-10) . However, in contrast, to TGF-0, TNF-a enhances IL-2-R expression, class II antigen expression, and IFN,y production by activated lymphocytes (9, 10). The contrasting immunoregulatory activities of these two proteins prompted studies to further define their immunoregulatory activities in vitro . In this report, we describe the dose-dependent inhibition of CTL generation by TGF-0 and the reversal of this inhibition by recombinant murine TNF-a (rMuTNF-a) . In addition, we demonstrate that TNF-a is an important cytokine involved in CTL development.