Transforming growth factor-β inhibits human antigen-specific CD4⁺ T cell proliferation without modulating the cytokine response

Transforming growth factor (TGF)-β has been demonstrated to play a key role in the regulation of the immune response, mainly by its suppressive function towards cells of the immune system. In humans, the effect of TGF-β on antigen-specific established memory T cells has not been investigated yet. In this study antigen-specific CD4⁺ T cell clones (TCC) were used to determine the effect of TGF-β on antigen-specific proliferation, the activation status of the T cells and their cytokine production. This study demonstrates that TGF-β is an adequate suppressor of antigen-specific T cell proliferation, by reducing the cell-cycle rate rather than induction of apoptosis. Addition of TGF-β resulted in increased CD69 expression and decreased CD25 expression on T cells, indicating that TGF-β is able to modulate the activation status of in vivo differentiated T cells. On the contrary, the antigen-specific cytokine production was not affected by TGF-β. Although TGF-β was suppressive towards the majority of the T cells, insensitivity of a few TCC towards TGF-β was also observed. This could not be correlated to differential expression of TGF-β signaling molecules such as Smad3, Smad7, SARA (Smad anchor for receptor activation) and Hgs (hepatocyte growth factor-regulated tyrosine kinase substrate). In summary, TGF-β has a pronounced inhibitory effect on antigen-specific T cell proliferation without modulating their cytokine production.