Abrogation of TGFβ Signaling in T Cells Leads to Spontaneous T Cell Differentiation and Autoimmune Disease

AbstractTargeted mutation of TGFβ1 in mice demonstrated that TGFβ1 is one of the key negative regulators of immune homeostasis, as its absence leads to activation of a self-targeted immune response. Nevertheless, because of the highly pleiotropic properties of TGFβ and the presence of TGFβ receptors on most cell types, its biologic role in the regulation of immune homeostasis is not yet understood. To limit the consequences of TGFβ effects to a single cell type, we developed a transgenic approach to abrogate the TGFβ response in key immune cells. Specifically, we expressed a dominant-negative TGFβ receptor type II under a T cell–specific promoter and created a mouse model where signaling by TGFβ is blocked specifically in T cells. Using this transgenic model, we show that T cell homeostasis requires TGFβ signaling in T cells