Overexpression of Total STAT1 During Lymphopenia-Induced Proliferation Leads to Decrease CD4 T Cell Survival

To preserve the size and diversity of the T cell repertoire throughout life, homeostatic mechanisms regulate both survival and proliferation through IL-7 and TCR signaling. IL-7 signals through a heterodimer receptor composed of the IL-7Rα and the γc chains. Binding of IL-7 to its receptor leads to activation of STAT5 and induction of target genes implicated in survival and proliferation signals. IL-7/IL-7R signaling can also activate STAT1 and STAT3 but the function of IL-7-dependent activation of these transcription factors is largely unknown. Under lymphopenic conditions, IL-7 modulates the expression levels of total STAT1 (t-STAT1) leading to an IL-7-dependent STAT1 signaling in addition to STAT5. We generated a transgenic mouse that overexpress STAT1 in CD4 and CD8 T cells to understand the contribution of IL-7-dependent STAT1 activation on T cell homeostasis in the setting of lymphopenia. We found that under lymphopenia-induced proliferation T cells from the STAT1 transgenic mouse upregulates t-STAT1 leading to diminish CD4 T cell survival. This mechanism could be a physiological mechanism to regulate the expansion of the CD4 T cell pool under lymphopenic conditions.