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Eur J Immunol. 2010 Mar;40(3):677-81. doi: 10.1002/eji.201040298.

c-Rel but not NF-kappaB1 is important for T regulatory cell development.

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Campbell Family Institute for Breast Cancer Research, Ontario Cancer Institute, Toronto, Ont., Canada.


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-kappaB via PKCtheta and the Bcl-10/CARMA1/MALT complex. Previous studies have shown that PKCtheta, Bcl-10 and CARMA1 are important for Treg development. It is unclear, however, whether different members of the NF-kappaB 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-kappaB1 (p50). Furthermore, using mixed bone marrow chimeras from WT and KO animals, we demonstrate that the requirement for PKCtheta, Bcl-10 and c-Rel is T-cell intrinsic, and cannot be rescued by the presence of WT cells. Therefore, c-Rel and NF-kappaB1 have differential roles in Treg development.

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