GSE106575
IL-7-dependent STAT1 activation limits homeostatic CD4+ T cell expansion
IL-7 regulates homeostatic mechanisms that maintain the overall size of the T cell pool throughout life. We show that, under steady-state conditions, IL-7 signaling is principally mediated by activation of signal transducers and activators of transcription 5 (STAT5). In contrast, under lymphopenic conditions, there is a modulation of STAT1 expression resulting in an IL-7-dependent STAT1 and STAT5 activation. Consequently, the IL-7-induced transcriptome is altered with enrichment of IFN-stimulated genes (ISGs). Moreover, STAT1 overexpression was associated with reduced survival in CD4+ T cells undergoing lymphopenia-induced proliferation (LIP). We propose a model in which T cells undergoing LIP upregulate STAT1 protein, "switching on" an alternate IL-7-dependent program. This mechanism could be a physiological process to regulate the expansion and size of the CD4+ T cell pool. During HIV infection, the virus could exploit this pathway, leading to the homeostatic dysregulation of the T cell pools observed in these patients. Overall design: Sorted naive CD4 T and CD8 T cells from WT or STAT1 transgenic mice were stimulated for 90 minutes with IL-7 or IFNg. Additonally CD4 T cells from WT or STAT1 trangenic or IL7Ra449F transgenic mice were stimulated for overnight with IL-7 or IFNg or IFNa4. Up to four biological replicates tested for each condition.