IL-7 signaling and CD127 receptor regulation in the control of T cell homeostasis

Abstract

IL-7 signaling and CD127 receptor regulation in the control of T cell homeostasis Florent Carrette1,3 and Charles D. Surh1,2 1Department of Immunology and Microbial Science, The Scripps Research Institute, La Jolla, CA 92037, USA 2WCU program, Division of IBB, POSTECH, Pohang, 790-784, Korea 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. 1. Introduction The overall size and composition of the T cell pool is maintained to be remarkably stable throughout most of the life in normal individuals. The ratio of naïve/memory T cell in the T cell pool is high in the young age, but gradually reverses with age from post-pubescent thymic atrophy combined with life-long immune response to pathogens. The long-term survival of nature T cells is sustained by signals from contact with cytokines and/or peptide/ MHC (pMHC) ligands [1, 2]. Indeed, homeostasis of naïve T cells is supported largely by IL-7 and contact with self-pMHC, while memory T cell homeostasis requires only IL-7 and IL-15. These signals maintain naïve T cells in an interphase whereas they induce occasional cell division of memory T cells [3, 4]. During the past decade, IL-7 has been identified as a, if not the, major homeostatic cytokine supporting the survival of various populations of mature T cell, not

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