Transforming growth factor type beta 1 (TGF-?1) down-regulates interleukin-2 production and up-regulates interleukin-2 receptor expression in a thymoma cell line

Abstract

Transforming growth factor type β1 (TGB‐β1) belongs to a family of polypeptides with regulatory effects on growth and differentiation of a variety of cell types. TGB‐β1 plays an important role in regulation of immune response by acting as a negative control signal for T cell proliferation through still unknown mechanisms. In this study we have analysed the effects of TGB‐β1 on EL 4–6.1, a variant of the murine EL 4 thymoma, which can be induced by phorbol 12‐myristate 13‐acetate (PMA) and/or interleukin 1 (IL‐1) to secrete interleukin 2 (IL‐2) and express IL‐2 receptors (IL‐2R). Using this defined model system, we show that TGB‐β1 simultaneously down‐regulates IL‐2 expression and up‐regulates the number of both high and low affinity IL‐2R. These changes correlate with changes at the mRNA level, suggesting an effect at the pre‐translational level. The specificity of both TGF‐β1 effects was demonstrated using a neutralizing antiserum to TGF‐β1. Our data also suggest that TGF‐β1 does not interfere with early activation signals of PMA and/or IL‐1. This model might be useful for elucidating the complex role of TGF‐β1 in the regulation of T cell responses.