Induction of IL-1β-converting enzyme-independent apoptosis by IL-2 in human T cell lines

Abstract

Our previous study demonstrated that IL-2 suppressed growth of human T cell lines, in which the suppression was observed with members among HTLV-I-infected T cell lines independent of IL-2 for growth. In this study, we examined the molecular mechanism of IL-2-induced growth suppression with two HTLV-I-infected T cell lines; TL-Oml expressing endogenously three subunits, i.e. α, β and γ chains, of the IL-2 receptor, and an MT-1 transfectant expressing the endogenous α and γ chains and exogenous β chain. Our analysis revealed that IL-2 induced apoptosis in both T cell lines. Experiments with inhibitors for the proteases responsible for apoptosis signals showed that caspase 1 (IL-1β-converting enzyme) was not involved in apoptosis induced by IL-2. Other MT-1 sublines introduced with mutant β chains demonstrated that IL-2-induced apoptosis required signals from both the serine-rich (S) region and acidic (A) region of the IL-2 receptor β chain, which are essential but not critical for IL-2-mediated cell growth respectively. Collectively, IL-2 functions not only on growth promotion and prevention of apoptosis but also on induction of apoptosis, which may be implicated in physiological regulation of immune reactions by controlling growth and activation of T cells.