Deletion Timing of Alleles during Hematopoiesis Determines the Degree of Peripheral CD4 T Cell Activation and Proliferation.

Capicua (CIC) is a transcriptional repressor that regulates several developmental processes. CIC deficiency results in lymphoproliferative autoimmunity accompanied by expansion of CD44CD62L effector/memory and follicular Th cell populations. Deletion of alleles in hematopoietic stem cells (-mediated knockout of ) causes more severe autoimmunity than that caused by the knockout of in CD4CD8 double positive thymocytes (-mediated knockout of ). In this study, we compared splenic CD4 T cell activation and proliferation between whole immune cell-specific -null () and T cell-specific -null () mice. Hyperactivation and hyperproliferation of CD4 T cells were more apparent in mice than in mice. CD4 T cells more rapidly proliferated and secreted larger amounts of IL-2 upon TCR stimulation than did CD4 T cells, while the TCR stimulation-induced activation of the TCR signaling cascade and calcium flux were comparable between them. Mixed wild-type and bone marrow chimeras also exhibited more apparent hyperactivation and hyperproliferation of -deficient CD4 T cells than did mixed wild-type and bone marrow chimeras. Taken together, our data demonstrate that CIC deficiency at the beginning of T cell development endows peripheral CD4 T cells with enhanced T cell activation and proliferative capability.