CD28/CTLA-4/B7 and CD40/CD40L costimulation and activation of regulatory T cells

Figure 1 Costimulatory requirements of Foxp3⁺ Treg cells. Treg cells, similar to Teff cells, depend on T cell receptor (TCR)-mediated recognition of an antigen for activation (signal 1). The requirements of Treg cells regarding the second, costimulatory signal are less clear. The exact pathways and necessary signals are still a matter of debate. So far, it is well established that Treg cells depend on CD28 and CD40L for their thymic development. Also, glucocorticoid-induced tumour necrosis factor related receptor (GITR) is stabilizing Foxp3 expression during maturation in the thymus. In order to get properly activated and to proliferate, triggering of OX40 and GITR, in concert with IL-2, was reported to be crucial. The induction of iTreg cells in the periphery is promoted by PD-1 signalling. The function of Treg cells depends on cytotoxic T lymphocyte antigen (CTLA)-4 and ICOS. See text for more details and references.