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Summary After their development in the thymus, mature T cells are maintained in the periphery by two sets of survival signals, namely TCR signals from contact with self-peptide/MHC ligands and the cytokine receptor signals from binding IL-7 and IL-15. These signals cooperate to maximize the utility of finite resources to support a diverse pool of mature T cells. It is becoming increasingly clear that multiple mechanisms exist to regulate expression of IL-7R at the transcriptional and post-translational levels. The interplay between TCR signals and IL-7R signals are also important in regulation of IL-7R expression. This review will focus on regulation of T cell homeostasis by IL-7R signaling, with an emphasis on the cross talk between signals from TCR and IL-7R.

In T cells, the PI3K pathway promotes proliferation and survival induced by Ag or growth factors, in part by inactivating the FOXO transcription factor 1. We now report that FOXO1 controls the expression of L-selectin, an essential homing molecule, in human T lymphocytes. This control is already operational in unprimed T cells and involves a transcriptional regulation process that requires the FOXO1 DNA-binding domain. Using transcriptional profiling, we demonstrate that FOXO1 also increases transcripts of EDG1 and EDG6, two sphingosine-1-phosphate receptors that regulate lymphocyte trafficking. Additionally, FOXO1 binds the promoter of the cell quiescence and homing regulator Krüppel-like factor 2 and regulates its expression. Together, these results reveal a new function of FOXO1 in the immune system and suggest that PI3K controls a coordinated network of transcription factors regulating both cell quiescence and homing of human T lymphocytes.