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.
D'Angeac
A D
AD
Unité INSERM 291, Montpellier, France.
Dornand
J
J
Emonds-Alt
X
X
Jullien
P
P
Garcia-Sanz
J A
JA
Erard
F
F
D000818:Animals; D015536:Down-Regulation / Q000187:drug effects*; D015870:Gene Expression / Q000235:genetics; D007375:Interleukin-1 / Q000494:pharmacology; D007376:Interleukin-2 / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D015375:Receptors, Interleukin-2 / Q000235:genetics / Q000378:metabolism*; D013601:T-Lymphocytes / Q000187:drug effects; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D013945:Thymoma / Q000378:metabolism / Q000473:pathology* / Q000648:ultrastructure; D013953:Thymus Neoplasms / Q000378:metabolism / Q000473:pathology* / Q000648:ultrastructure; D016212:Transforming Growth Factor beta / Q000494:pharmacology* / Q000502:physiology; D015854:Up-Regulation / Q000187:drug effects*
D007375:Interleukin-1; D007376:Interleukin-2; D012333:RNA, Messenger; D015375:Receptors, Interleukin-2; D016212:Transforming Growth Factor beta; D013755:Tetradecanoylphorbol Acetate