Abrogation of TGFβ signaling in T cells leads to spontaneous T cell differentiation and autoimmune disease

Targeted mutation of TGF beta 1 in mice demonstrated that TGF beta 1 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 TGF beta and the presence of TGF beta receptors on most cell types, its biologic role in the regulation of immune homeostasis is not yet understood. To limit the consequences of TGF beta effects to a single cell type, we developed a transgenic approach to abrogate the TGF beta response in key immune cells. Specifically, we expressed a dominant-negative TGF beta receptor type II under a T cell-specific promoter and created a mouse model where signaling by TGF beta is blocked specifically in T cells. Using this transgenic model, we show that T cell homeostasis requires TGF beta signaling in T cells.