Constitutive activation of STAT5 supersedes the requirement for cytokine and TCR engagement of CD4+ T cells in steady-state homeostasis

Devon K. Taylor, Patrick T. Walsh, David F. LaRosa, Jidong Zhang, Matthew A. Burchill, Michael A. Farrar, Laurence A. Turka

Research output: Contribution to journalArticlepeer-review

13 Scopus citations

Abstract

The transcription factor STAT5 is one of several signaling mediators activated via common γ-chain cytokine receptors. As such, it plays an important role in lymphocyte survival and proliferation during normal homeostasis as well as under lymphopenic conditions. Transgenic mice expressing a constitutively activated form of STAT5b have been shown previously to contain increased numbers of peripheral CD4+CD25- T cells. To define the mechanism(s) for this occurrence, we have used adoptive transfer studies to examine the effects of STAT5 activity on steady-state CD4+ T cell homeostasis. We observed that constitutive STAT5 signaling induced 4- to 7-fold increased levels of basal steady-state proliferation, which was accompanied by a comparable increase in T cell recovery. Most strikingly, steady-state CD4 T cell proliferation occurred independently of both MHC class II and IL-15. These observations demonstrate that the STAT5-driven pathway is important to lymphocyte homeostasis and can supersede the need for both TCR engagement and cytokine stimulation. This suggests that the need for TCR stimulation to induce common γ-chain cytokine receptor expression, and thus STAT5 activation, is a key factor in maintaining normal CD4+ T cell homeostasis.

Original languageEnglish (US)
Pages (from-to)2216-2223
Number of pages8
JournalJournal of Immunology
Volume177
Issue number4
DOIs
StatePublished - Aug 15 2006

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