c-Rel but not NF-κB1 is important for T regulatory cell development

Regulatory T (Treg) cells are crucial for maintaining peripheral tolerance and controlling T-cell responses. The generation of Treg in the thymus requires TCR triggering and CD28 costimulation. Engagement of these receptors induces a number of signalling pathways, including the activation of NF-kappa B via PKC theta and the Bcl-10/CARMA1/MALT complex. Previous studies have shown that PKC theta, Bcl-10 and CARMA1 are important for Treg development. It is unclear, however, whether different members of the NF-kappa B family contribute to Treg development or homeostasis. In this study, we show that Treg numbers are reduced in the absence of c-Rel but not NF-kappa B1 (p50). Furthermore, using mixed bone marrow chimeras from WT and KO animals, we demonstrate that the requirement for PKC theta, Bcl-10 and c-Rel is T-cell intrinsic, and cannot be rescued by the presence of WT cells. Therefore, c-Rel and NF-kappa B1 have differential roles in Treg development.