Zfp281 is a negative regulator of maintaining pluripotency for embryonic stem cells(ESC).However,its role in other cell types is poorly understood.We therefore generated Zfp281 conditional knockout mice in which the function of Zfp281 gene was conditionally disrupted by CD4Cre transgene.Our data showed that while Zfp281 was dispensable for T cell development,it is required for the activation and immune responses of CD4+T cells.Furthermore,genome-wide expression profiling and chromatin-immunoprecipitation assay identified that Zfp281 negatively regulated CTLA-4 expression by directly binding its promoter.In the model of L.monocytogenes infection,Zfp281 promoted T cell responses to bacterial responses.These findings identify Zfp281 as an important regulator of the activation and function in CD4+T cells.