TGFβ1 deficiency does not affect the generation and maintenance of CD4⁺CD25⁺FOXP3⁺ putative T_reg cells, but causes their numerical inadequacy and loss of regulatory function

TGFβ1 is considered to be required for peripheral maintenance of CD4⁺CD25⁺FOXP3⁺ T_reg cells. However, we demonstrate no reduction in the percentage of such T cells in the spleens and thymi of Tgfb1^-/- mice. Although putative T_reg cells, characterized as CD4⁺CD25⁺FOXP3⁺CD62L⁺ T cells, are increased in Tgfb1^-/- mice, they may be inadequate to control activated T cells since the ratio of activated T cells:putative T_reg cells is several-fold higher in Tgfb1^-/- mice than in control mice. We further show that whereas Tgfb1^-/- mice that express a chicken OVA-specific TCR transgene (DO11.10) have an increase in putative T_reg cells, there are no detectable CD4⁺CD25⁺ T cells in the spleens of DO11.10 Rag1^-/- mice suggesting that T_reg-cell generation is self-antigen dependent regardless of whether they express Tgfb1. Finally, we demonstrate that Tgfb1^-/- T cells remain responsive to the suppressive effect of TGFβ1 in vitro. These data suggest that TGFβ1 is required for the regulatory function of T_reg cells to prevent activation of T cells and autoimmunity.