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Stat5 is required for IL-2-induced cell cycle progression of peripheral T cells
R Moriggl1, D J Topham, S Teglund
1Howard Hughes Medical Institute, and Department of Biochemistry, St. Jude Children's Research Hospital, Memphis, Tennessee 38105, USA.
Abstract:
Many cytokines activate two highly homologous Stat proteins, 5a and 5b. Mice deficient in both genes lack all growth hormone and prolactin functions but retain functions associated with cytokines such as erythropoietin. Here, we demonstrate that, while lymphoid development is normal, Stat5a/b mutant peripheral T cells are profoundly deficient in proliferation and fail to undergo cell cycle progression or to express genes controlling cell cycle progression. In addition, the mice lack NK cells, develop splenomegaly, and have T cells with an activated phenotype, phenotypes seen in IL-2 receptor beta chain-deficient mice. These phenotypes are not seen in mice lacking Stat5a or Stat5b alone. The results demonstrate that the Stat5 proteins, redundantly, are essential mediators of IL-2 signaling in T cells.
Insights
Signal transducer and activator of transcription (Stat) 5a and 5b proteins are essential for T cell proliferation and cell cycle progression. Redundantly, Stat5 proteins mediate interleukin-2 (IL-2) signaling in T cells.
Area of Science:
- Immunology
- Molecular Biology
- Cell Biology
Background:
- Cytokines activate homologous Stat5a and Stat5b proteins.
- Stat5a/b deficient mice lack growth hormone and prolactin functions but retain erythropoietin functions.
Purpose of the Study:
- To investigate the role of Stat5a and Stat5b proteins in T cell function and lymphoid development.
- To determine if Stat5a and Stat5b redundantly mediate interleukin-2 (IL-2) signaling in T cells.
Main Methods:
- Generation and analysis of Stat5a/b double-mutant mice.
- Assessment of T cell proliferation, cell cycle progression, and gene expression.
- Phenotypic analysis of lymphoid organs and immune cell populations.
Main Results:
- Stat5a/b mutant T cells show profound deficiency in proliferation and cell cycle progression.
- Mutant mice lack NK cells, develop splenomegaly, and exhibit activated T cell phenotypes.
- These phenotypes are specific to the double deficiency, not seen in single Stat5a or Stat5b mutants.
Conclusions:
- Stat5a and Stat5b proteins redundantly mediate IL-2 signaling in T cells.
- Stat5 proteins are essential for T cell proliferation, cell cycle progression, and NK cell development.