Evaluation of Specific Purified TCR Effect on the Immunoregulatory Potential of TGF-beta

Transforming growth factor beta (TGF-b) is a mediator released by nearly all cell types. It has suppression activity on the immune system, but exactly how this effect is carried out is not clear. Previous experiments showed that IgG interacts with or carriers active TGF-b, that could suppresses cytotoxic T-cell responses to an immunogenic tumor in mice. Since T cell receptor (TCR) has structural similarities with IgG, we asked the question whether a specific TCR could interfere with and enhance the suppressive effect of TGF-b on T-cell proliferation. T-cell lines were established by limiting dilution and specific TCR were extracted and purified. Mixed lymphocyte reaction (MLR) was carried out using DA (RT1a) vs. LEW (RT11) lymph node cells and DA vs. PVG (RT1u) lymph node cells. DA cells were used as responder cells and PVG/LEW as stimulator cells. Proliferation of DA cells was examined with different concentration of TGF-b by adding 1mci 3H-thymidine 24 hours prior to harvesting the cells. The results showed that the presence of a specific TCR does not have any effect on the percentage of suppression when already fully suppressed by TGF-b. However, it does have an effect on TGF-b stimulated suppression under certain conditions. When TCR was added at the same concentration as TGF-b (1-2 ng/ml), inhibited TGF-b stimulated suppression of proliferation, but when added at higher concentration than TGF-b, this effect disappeared, and the proliferation was suppressed in the same way, as TCR was absent. Thus, TCR interaction with TGF-b could play an important role in the homeostasis of immunity by augmenting the proliferation of activated dominant lymphocyte clones. This would promote suppression of activation/proliferation of new specific antigen-reactive clones that may arise during ongoing immunity, and also suppressing some autoimmune diseases