TGF-beta, T-cell tolerance and anti-CD3 therapy

Recent studies by Chatenoud and co-workers suggest that non-mitogenic F(ab′)2 fragments of anti-CD3 antibodies, which cannot bind the Fc receptor, induce a prolonged period of tolerance and prevent diabetes in nonobese diabetic (NOD) mice. Tolerance is established by regulatory T cells through the production of transforming growth factor-β1 (TGF-β1), but the mechanism by which TGF-β1 confers this activity is unclear. Analysis of mice deficient in TGF-β1 suggests that TGF-β1 raises the threshold at which intracellular calcium activates T cells to a level that prevents an autoimmune response.