Distinct IL-2 Receptor Signaling Pattern in CD4+CD25 + Regulatory T Cells

Steven J. Bensinger, Patrick T. Walsh, Jidong Zhang, Martin Carroll, Ramon Parsons, Jeffrey C. Rathmell, Craig B. Thompson, Matthew A. Burchill, Michael A. Farrar, Laurence A. Turka

Research output: Contribution to journalArticlepeer-review

213 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)5287-5296
Number of pages10
JournalJournal of Immunology
Volume172
Issue number9
DOIs
StatePublished - May 1 2004

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