Distinct effects of STAT5 activation on CD4+ and CD8+ T cell homeostasis: development of CD4+CD25+ regulatory T cells versus CD8+ memory T cells.
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.
Burchill
Matthew A
MA
Center for Immunology, Cancer Center, Department of Laboratory Medicine and Pathology, University of Minnesota, Minneapolis, MN 55455, USA.
Goetz
Christine A
CA
Prlic
Martin
M
O'Neil
Jennifer J
JJ
Harmon
Ian R
IR
Bensinger
Steven J
SJ
Turka
Laurence A
LA
Brennan
Paul
P
Jameson
Stephen C
SC
Farrar
Michael A
MA
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
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