Distinct Effects of STAT5 Activation on CD4+ and CD8 + T Cell Homeostasis: Development of CD4+CD25+ Regulatory T Cells versus CD8+ Memory T Cells

Matthew A. Burchill, Christine A. Goetz, Martin Prlic, Jennifer J. O'Neil, Ian R. Harmon, Steven J. Bensinger, Laurence A. Turka, Paul Brennan, Stephen C. Jameson, Michael A. Farrar

Research output: Contribution to journalArticle

158 Scopus citations

Abstract

Using transgenic mice that express a constitutively active version of STAT5b, we demonstrate that STAT5 plays a key role in governing B cell development and T cell homeostasis. STAT5 activation leads to a 10-fold increase in pro-B, but not pro-T, cells. Conversely, STAT5 signaling promotes the expansion of mature αβ T cells (6-fold increase) and γδ and NK T cells (3- to 4-fold increase), but not of mature B cells. In addition, STAT5 activation has dramatically divergent effects on CD8+ vs CD4+ T cells, leading to the selective expansion of CD8+ memory-like T cells and CD4+CD25+ regulatory T cells. These results establish that activation of STAT5 is the primary mechanism underlying both IL-7/IL-15-dependent homeostatic proliferation of naive and memory CD8+ T cells and IL-2-dependent development of CD4+CD25+ regulatory T cells.

Original languageEnglish (US)
Pages (from-to)5853-5864
Number of pages12
JournalJournal of Immunology
Volume171
Issue number11
DOIs
StatePublished - Dec 1 2003

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