Transforming growth factor-beta induces apoptosis in activated murine T cells through the activation of caspase 1-like protease

Transforming growth factor-beta (TGF-beta) has been known as a potent immun osuppressive cytokine that can induce apoptosis in lymphoid cells. We estab lished an IL-2-independent cell line, CTLL-2A, from murine T cell line CTLL -2. CTLL-2A expressed higher levels of CD95, CD69, and CD18 molecules than CTLL-2 did, suggesting a more activated state in CTLL-2A than in the CTLL-2 by phenotype. Exposing both CTLL-2 and CTLL-2A to TGF-beta results in diff erential apoptosis patterns defined by DNA fragmentation and plasma membran e alteration. Among the bcl-2 family members, bcl-2, bcl-w, and bcl-x(L) we re also differently expressed in these two cell lines. In CTLL-2A, bcl-x(L) was amplified as a major anti-apoptotic molecule, and TGF-beta-induced cel l death was more enhanced than in the original cell line. Caspase 1-like pr otease was activated by TGF-beta treatment and consequently it cleaved bcl- x(L) in CTLL-2A. TGF-beta-induced DNA fragmentation and cleavage of bcl-x(L ), were inhibited by pretreatment with tetra peptide caspase 1 inhibitor, Y VAD.cmk. These findings suggest that TGF-beta induces cell death in activat ed murine T cells through cleavage of bcl-x(L) via activated caspase 1-like protease, which may act as an important executor in that process. (C) 2000 Academic Press.