Transforming growth factor-beta s are equipotent growth inhibitors of interleukin-1-induced thymocyte proliferation.
The effects of two forms of transforming growth factor-beta, TGF-beta 1 and TGF-beta 2, upon the proliferative response of murine thymocytes were investigated in this study. TGF-beta 1 and TGF-beta 2 were found to be equipotent growth inhibitors of interleukin-1 (IL-1)- and phytohemagglutinin (PHA)-stimulated thymocytes when added at the initiation of the cultures. These factors suppressed the proliferative response in a dose-dependent fashion between 0.4 and 100 pM. The proliferative response was maximally inhibited (90% inhibition) at 100 pM. The half-maximal inhibitory dose (ID50) was 6 and 4 pM for TGF-beta 1 and TGF-beta 2, respectively. These factors were less effective or ineffective at suppressing the proliferation of thymocytes which had been prestimulated for 24 to 48 hr by IL-1 and PHA. Neither factor inhibited interleukin-2 (IL-2)-dependent thymocyte proliferation or the proliferation of an IL-2-dependent cytotoxic T cell line (CTL-L), suggesting that the anti-proliferative actions of these factors was by inhibition of cellular events triggered by IL-1. Furthermore, anti-TGF-beta 1 antibodies did neutralize the biological actions of TGF-beta 1 and these antibodies did block the binding of 125I-labeled TGF-beta 1 to cell surface receptors showing that the inhibitory action is mediated through specific receptors for TGF-beta 1 on thymocytes. These antibodies, however, did not neutralize the anti-proliferative action of TGF-beta 2. Although TGF-beta 1 and TGF-beta 2 exhibit very similar biological activities, these molecules are antigenically different and, therefore, have different tertiary structures.
D000818:Animals; D066298:In Vitro Techniques; D007375:Interleukin-1 / Q000037:antagonists & inhibitors*; D008213:Lymphocyte Activation / Q000187:drug effects*; D051379:Mice; D008970:Molecular Weight; D009500:Neutralization Tests; D010455:Peptides / Q000145:classification / Q000494:pharmacology*; D011956:Receptors, Cell Surface / Q000502:physiology; D018125:Receptors, Transforming Growth Factor beta; D013601:T-Lymphocytes / Q000502:physiology*; D013950:Thymus Gland / Q000166:cytology; D015291:Transforming Growth Factors
D007375:Interleukin-1; D010455:Peptides; D011956:Receptors, Cell Surface; D018125:Receptors, Transforming Growth Factor beta; D015291:Transforming Growth Factors