Zhang, Z., Liu, W., Zhao, L., Huang, Z., Chen, X., Ma, N., Xu, J., Zhang, W., Zhang, Y. (2017) Rb1 promotes T cell maturation from premature apoptosis by inhibiting E2F1. Development (Cambridge, England). 145(1).
T lymphocytes are key cellular components of an acquired immune system and play essential roles in cell-mediated immunity. T cell development occurs in the thymus where 95% of immature thymocytes are eliminated via apoptosis. It is known that mutation of Zeb1, one of the retinoblastoma 1 (Rb1) target genes, results in a decrease in the number of immature T cells in mice. E2F1, an RB1-interacting protein, has been shown to regulate mature T cell development by interfering with thymocyte apoptosis. However, whether Rb1 regulates thymocyte development in vivo still needs to be further investigated. Here, we use a zebrafish model to investigate the role of Rb1 in T cell development. We show that Rb1-deficient fish exhibit a significant reduction in T cell number during early development that it is attributed to the accelerated apoptosis of immature T cells in a caspase-dependent manner. We further show that E2F1 overexpression could mimic the reduced T lymphocytes phenotype of Rb1 mutants, and E2F1 knockdown could rescue the phenotype in Rb1-deficient mutants. Collectively, our data indicate that the Rb1-E2F1-caspase axis is crucial for protecting immature T cells from apoptosis during early T lymphocyte maturation.