P53 prevents maturation of T cell development to the immature CD4 −CD8 + stage in Bcl11b−/− mice

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Signaling pathways such as the pre-TCR and Wnt pathways regulate α/β T cell differentiation in thymus. Mice lacking an essential component of the pre-TCR exhibit arrest at the (CD4 −CD8 −) (CD44 −CD25 +) stage (DN3) of thymocyte development, and introduction of p53 deficiency into those mice abrogates this arrest, resulting in transition to the (CD4 +CD8 +) double-positive (DP) stage. This paper examines the effect of inactivation of p53 on thymocyte development in Bcl11b −/− mice that exhibit arrest at the DN3 or (CD4 −CD8 +) immature single-positive (ISP) stage. No DP thymocytes were detected in thymocytes of adoptive transfer experiments in scid mice that were derived from p53 −/− Bcl11b −/− precursors but ISP thymocytes increased in the proportion and in the cell number approximately three times higher than those from Bcl11b −/− precursors. Consistently, the level of apoptosis decreased to the level of wild-type precursors. These results suggest that inactivation of p53 is sufficient for DN3 thymocytes to differentiate into the ISP, but not to DP, stage of thymocyte development in Bcl11b −/− mice. This provides evidence for a novel p53-mediated checkpoint that regulates the transition from the DN3 to ISP stage of thymocyte development.