TGFb regulates the CD41CD251 T-cell pool and the expression of Foxp3 in vivo

Factors influencing the development of CD41CD251 T-cells in vivo are poorly understood. In order to investigate the contribution of TGFb1 to the development and function of CD41CD251 T-cells, we generated a gain of function mutation resulting in the overexpression of an active form of TGFb1 in T-cells under control of the human CD2 promoter. In peripheral lymphoid organs and in the thymus, the frequency of CD41CD251 T-cells was increased in transgenic mice. This appeared to be due to an autocrine effect of TGFb on T-cells, since concomitant impairment of TGFb-signaling in double transgenic mice resulted in a phenotype similar to wild type. In contrast, in single transgenic mice with impaired TGFb-signaling in T-cells, CD41CD251 T-cell numbers were reduced in peripheral lymphoid organs but not in the thymus. In addition, TGFb was found to regulate the expression of Foxp3 in vivo, a transcription factor essential for the generation and function of regulatory T-cells. In CD41CD251 T-cells, TGFb1 increased the expression of Foxp3, whereas a decreased expression was seen in CD41CD251 T-cells with impaired TGFb-signaling. TGFb1 induced the expression of IL-10 in transgenic T-cells, but the increased in vitro suppressive capacity observed in transgenic CD41CD251 T-cells was due to the secretion of TGFb and not IL-10. Therefore, our study provides in vivo evidence for a role of TGFb in the homeostasis of CD41CD251 T-cells.