TGFbeta1 is not essential for generation and maintenance of natural Treg cells (128.10)

Abstract Natural CD4+CD25+FOXP3+ Treg cells serve as powerful regulators of autoimmunity. Hence, there has been a great deal of interest in understanding their regulation. TGFβ1 is considered to be required for peripheral maintenance of Treg cells. However, we demonstrate an increase in the percentage of FOXP3+ Treg cells in the spleens and thymi of Tgfb1−/− mice. Despite this abundance of Treg cells, Tgfb1−/− mice develop a marked expansion of activated T cells in their lymphoid organs, suggesting that activated Tgfb1−/− T cells may not be amenable to suppression any more. However, we demonstrate that Tgfb1−/− T cells do remain responsive to the suppressive effect of TGFβ1 in vitro, suggesting that the absence of TGFβ1 production by Treg cells likely leads to their loss of regulatory function. Finally, we show that whereas Tgfb1−/− mice that express a chicken OVA-specific TCR transgene (DO11.10) have an increase in Treg cells, there are no detectable CD4+CD25+ T cells in the spleens of DO11.10 Rag1−/− mice that have no self-reactive T-cells, regardless of whether they express Tgfb1. This suggests that Treg-cell generation is self-antigen dependent and that TGFβ1 is not required for Treg-cell generation and maintenance. We contemplate that TGFβ1 is likely required for the regulatory function of Treg cells to prevent activation of T cells and autoimmunity.