Distinct IL-2 Receptor Signaling Pattern in CD4+CD25+ Regulatory T Cells
Copyright policy )Distinct IL-2 Receptor Signaling Pattern in CD4+CD25+ Regulatory T Cells
Abstract Despite expression of the high-affinity IL-2R, CD4+CD25+ regulatory T cells (Tregs) are hypoproliferative upon IL-2R stimulation in vitro. However the mechanisms by which CD4+CD25+ T cells respond to IL-2 signals are undefined. In this report, we examine the cellular and molecular responses of CD4+CD25+ Tregs to IL-2. IL-2R stimulation results in a G1 cell cycle arrest, cellular enlargement and increased cellular survival of CD4+CD25+ T cells. We find a distinct pattern of IL-2R signaling in which the Janus kinase/STAT pathway remains intact, whereas IL-2 does not activate downstream targets of phosphatidylinositol 3-kinase. Negative regulation of phosphatidylinositol 3-kinase signaling and IL-2-mediated proliferation of CD4+CD25+ T cells is inversely associated with expression of the phosphatase and tensin homologue deleted on chromosome 10, PTEN.
- University of Pennsylvania United States
- University of Minnesota Morris United States
- King’s University United States
- University of Chicago United States
- Abramson Cancer Center United States
Mice, Inbred BALB C, Cell Survival, PTEN Phosphohydrolase, Receptors, Antigen, T-Cell, Down-Regulation, Receptors, Interleukin-2, Protein Serine-Threonine Kinases, Growth Inhibitors, Mice, Phosphatidylinositol 3-Kinases, Proto-Oncogene Proteins, Animals, Interleukin-2, Phosphorylation, Protein Tyrosine Phosphatases, Proto-Oncogene Proteins c-akt, Cell Division, Cells, Cultured, Oligonucleotide Array Sequence Analysis, Phosphoinositide-3 Kinase Inhibitors
Mice, Inbred BALB C, Cell Survival, PTEN Phosphohydrolase, Receptors, Antigen, T-Cell, Down-Regulation, Receptors, Interleukin-2, Protein Serine-Threonine Kinases, Growth Inhibitors, Mice, Phosphatidylinositol 3-Kinases, Proto-Oncogene Proteins, Animals, Interleukin-2, Phosphorylation, Protein Tyrosine Phosphatases, Proto-Oncogene Proteins c-akt, Cell Division, Cells, Cultured, Oligonucleotide Array Sequence Analysis, Phosphoinositide-3 Kinase Inhibitors
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