Transforming Growth Factor-β Induces Apoptosis in Activated Murine T Cells through the Activation of Caspase 1-like Protease

Transforming growth factor-β (TGF-β) has been known as a potent immunosuppressive cytokine that can induce apoptosis in lymphoid cells. We established 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-β results in differential apoptosis patterns defined by DNA fragmentation and plasma membrane alteration. Among the bcl-2 family members, bcl-2, bcl-w, and bcl-xL were also differently expressed in these two cell lines. In CTLL-2A, bcl-xL was amplified as a major anti-apoptotic molecule, and TGF-β-induced cell death was more enhanced than in the original cell line. Caspase 1-like protease was activated by TGF-β treatment and consequently it cleaved bcl-xL in CTLL-2A. TGF-β-induced DNA fragmentation and cleavage of bcl-xL were inhibited by pretreatment with tetra peptide caspase 1 inhibitor, YVAD.cmk. These findings suggest that TGF-β induces cell death in activated murine T cells through cleavage of bcl-xL via activated caspase 1-like protease, which may act as an important executor in that process.