TRANSFORMING GROWTH-FACTOR TYPE BETA-1 (TGF-BETA-1) DOWN-REGULATES INTERLEUKIN-2 PRODUCTION AND UP-REGULATES INTERLEUKIN-2 RECEPTOR EXPRESSION IN A THYMOMA CELL-LINE

Transforming growth factor type beta-1 (TGB-beta-1) belongs to a family of polypeptides with regulatory effects on growth and differentiation of a variety of cell types. TGB-beta-1 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-beta-1 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-beta-1 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-beta-1 effects was demonstrated using a neutralizing antiserum to TGF-beta-1. Our data also suggest that TGF-beta-1 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-beta-1 in the regulation of T cell responses.