Transforming growth factor‐β2 induces apoptosis of murine T cell clones without down‐regulating bcl‐2 mRNA expression

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Abstract
Transforming growth factor‐β (TGFβ) is a potent immunosuppressive cytokine which inhibits the antigen (Ag)‐dependent expansion of T cells both in vitro and in vivo by mechanisms not well defined yet. Here we report that exposure of interleukin (IL)‐2‐dependent T cell lines to TGFβ2 results in apoptosis defined by morphology, nucleosomal size DNA fragmentation and in situ DNA end labeling. TGFβ2‐induced T cell apoptosis showed the following characteristics: (1) in contrast to the rapid evolution of apoptosis following IL‐2 deprivation, apoptosis of T cells triggered by TGFβ2 was delayed; (2) cycloheximide prevented TGFβ2‐induced apoptosis of CTLL‐2 but not of OVA‐7 T helper cells; (3) in contrast to apoptosis following IL‐2 deprivation, TGFβ2‐mediated T cell apoptosis was not associated with decreased expression of the proto‐oncogenes, bcl‐2 or c‐myc; (4) TGFβ2‐induced apoptosis was not restricted to IL‐2‐dependent T cell lines since the IL‐4‐dependent T cell line, CT.4S, as well as EL4 lymphoma cells, which grow independently of exogenous IL‐2, were also susceptible to TGFβ2‐mediated apoptosis. Taken together, these data may present a novel mechanism of TGFβ2‐mediated suppression of T cell expansion in response to Ag and IL‐2, the activation of the endogenous death program of apoptosis, which appears to operate independently of direct interactions of TGFβ2 with the IL‐2/IL‐2 receptor system.

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