The development of regulatory T cells, which naturally suppress immune responses, thus preventing autoimmune diseases, such as type 1 diabetes, is discussed in a paper published online this week in Nature Immunology.

All T immune cells express a receptor molecule called the TCR. Most T cells with a TCR that could potentially cause autoimmunity die during development but some are required to become regulatory T cells. How such cells avoid cell death and develop into regulatory cells is not understood.

Michael A. Farrar and colleagues find that mouse regulatory T cells specifically express three molecules - GITR, OX40 and TNFR2 - on their surface and the activation of these molecules rescues the developing regulatory T cells from death. By regulating the scope of signals transmitted via the TCR and saving regulatory T cells from certain death, GITR, OX40 and TNFR2 ensure that the immune system remains tolerant to the body and avoids autoimmune diseases.