Rb1 promotes T cell maturation from premature apoptosis by inhibiting E2F1 [RESEARCH ARTICLE]

Zili Zhang, Wei Liu, Lingfeng Zhao, Zhibin Huang, Xiaohui Chen, Ning Ma, Jin Xu, Wenqing Zhang, and Yiyue Zhang

T lymphocytes are key cellular components of 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 RB1 target genes, resulted in immature T cell decrease in mice. E2F1, an RB1 interacting protein, has been shown to regulate mature T cell development by interfering with thymocyte apoptosis. However, whether Rb1 regulate thymocyte development in vivo is still need to be further investigated. Here we use zebrafish model to investigate the role of Rb1 in T cell development. We show that Rb1-deficient fish exhibit a significant reduction of T cells during early development and it is attributed to the accelerated apoptosis of immature T cell 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 indicated that Rb1-E2F1-Caspase axis is crucial for protecting immature T cells from apoptosis during early T lymphocyte maturation.

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