title: Distinct effects of STAT5 activation on CD4+ and CD8+ T cell homeostasis: development of CD4+CD25+ regulatory T cells versus CD8+ memory T cells.
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 alphabeta T cells (6-fold increase) and gammadelta 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.
authors.affiliation: Center for Immunology, Cancer Center, Department of Laboratory Medicine and Pathology, University of Minnesota, Minneapolis, MN 55455, USA.
authors.forename: Matthew A
authors.initials: MA
authors.lastname: Burchill
authors.forename: Christine A
authors.initials: CA
authors.lastname: Goetz
authors.forename: Martin
authors.initials: M
authors.lastname: Prlic
authors.forename: Jennifer J
authors.initials: JJ
authors.lastname: O'Neil
authors.forename: Ian R
authors.initials: IR
authors.lastname: Harmon
authors.forename: Steven J
authors.initials: SJ
authors.lastname: Bensinger
authors.forename: Laurence A
authors.initials: LA
authors.lastname: Turka
authors.forename: Paul
authors.initials: P
authors.lastname: Brennan
authors.forename: Stephen C
authors.initials: SC
authors.lastname: Jameson
authors.forename: Michael A
authors.initials: MA
authors.lastname: Farrar
mesh_terms: D000818:Animals; D016175:B-Lymphocyte Subsets / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology* / Q000276:immunology / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology* / Q000276:immunology / Q000378:metabolism; D002454:Cell Differentiation / Q000235:genetics / Q000276:immunology; D002455:Cell Division / Q000235:genetics / Q000276:immunology; D003433:Crosses, Genetic; D004268:DNA-Binding Proteins / Q000378:metabolism / Q000502:physiology*; D006706:Homeostasis / Q000235:genetics / Q000276:immunology*; D007156:Immunologic Memory / Q000235:genetics; D007694:Killer Cells, Natural / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D051379:Mice; D008822:Mice, Transgenic; D008894:Milk Proteins; D011948:Receptors, Antigen, T-Cell / Q000037:antagonists & inhibitors / Q000502:physiology; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000378:metabolism; D015375:Receptors, Interleukin-2 / Q000096:biosynthesis; D050799:STAT5 Transcription Factor; D015398:Signal Transduction / Q000235:genetics / Q000276:immunology; D016176:T-Lymphocyte Subsets / Q000166:cytology* / Q000276:immunology / Q000378:metabolism; D050378:T-Lymphocytes, Regulatory / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D015534:Trans-Activators / Q000378:metabolism / Q000502:physiology*; D015854:Up-Regulation / Q000235:genetics / Q000276:immunology
chemical_list: D004268:DNA-Binding Proteins; D008894:Milk Proteins; D011948:Receptors, Antigen, T-Cell; D016692:Receptors, Antigen, T-Cell, gamma-delta; D015375:Receptors, Interleukin-2; D050799:STAT5 Transcription Factor; C494096:Stat5b protein, mouse; D015534:Trans-Activators