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.
Publication types
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Comparative Study
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Animals
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B-Lymphocyte Subsets / cytology
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B-Lymphocyte Subsets / immunology
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B-Lymphocyte Subsets / metabolism
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CD4-Positive T-Lymphocytes / cytology*
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CD4-Positive T-Lymphocytes / immunology
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CD4-Positive T-Lymphocytes / metabolism
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CD8-Positive T-Lymphocytes / cytology*
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CD8-Positive T-Lymphocytes / immunology
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CD8-Positive T-Lymphocytes / metabolism
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Cell Differentiation / genetics
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Cell Differentiation / immunology
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Cell Division / genetics
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Cell Division / immunology
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Crosses, Genetic
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DNA-Binding Proteins / metabolism
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DNA-Binding Proteins / physiology*
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Homeostasis / genetics
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Homeostasis / immunology*
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Immunologic Memory* / genetics
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Killer Cells, Natural / cytology
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Killer Cells, Natural / immunology
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Killer Cells, Natural / metabolism
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Mice
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Mice, Transgenic
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Milk Proteins*
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Receptors, Antigen, T-Cell / antagonists & inhibitors
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Receptors, Antigen, T-Cell / physiology
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Receptors, Antigen, T-Cell, gamma-delta / metabolism
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Receptors, Interleukin-2 / biosynthesis
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STAT5 Transcription Factor
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Signal Transduction / genetics
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Signal Transduction / immunology
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T-Lymphocyte Subsets / cytology*
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T-Lymphocyte Subsets / immunology
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T-Lymphocyte Subsets / metabolism
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T-Lymphocytes, Regulatory / cytology
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T-Lymphocytes, Regulatory / immunology
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T-Lymphocytes, Regulatory / metabolism
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Trans-Activators / metabolism
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Trans-Activators / physiology*
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Up-Regulation / genetics
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Up-Regulation / immunology
Substances
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DNA-Binding Proteins
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Milk Proteins
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Receptors, Antigen, T-Cell
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Receptors, Antigen, T-Cell, gamma-delta
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Receptors, Interleukin-2
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STAT5 Transcription Factor
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Stat5b protein, mouse
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Trans-Activators