Open AccessCutting Edge: The Phosphoinositide 3-Kinase p110δ Is Critical for the Function of CD4+CD25+Foxp3+ Regulatory T Cells
Author(s) -
Daniel T. Patton,
Oliver A. Garden,
Wayne Pearce,
Louise E. Clough,
Clare R Monk,
Eva Leung,
Wendy C. Rowan,
Sara Sancho,
Lucy S. K. Walker,
Bart Vanhaesebroeck,
Klaus Okkenhaug
Publication year - 2006
Publication title -
the journal of immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.737
H-Index - 372
eISSN - 1550-6606
pISSN - 0022-1767
DOI - 10.4049/jimmunol.177.10.6598
Subject(s) - foxp3 , il 2 receptor , microbiology and biotechnology , adoptive cell transfer , regulatory t cell , cd28 , peripheral tolerance , biology , immunology , chemistry , immune tolerance , t cell , antigen , immune system
CD4+CD25+Foxp3+ regulatory T cells (Tregs) contribute to the maintenance of peripheral tolerance by inhibiting the expansion and function of conventional T cells. Treg development and homeostasis are regulated by the Ag receptor, costimulatory receptors such as CD28 and CTLA-4, and cytokines such as IL-2, IL-10, and TGF-beta. Here we show that the proportions of Tregs in the spleen and lymph nodes of mice with inactive p110delta PI3K (p110deltaD910A/D910A) are reduced despite enhanced Treg selection in the thymus. p110deltaD910A/D910A CD4+CD25+Foxp3+ Tregs showed attenuated suppressor function in vitro and failed to secrete IL-10. In adoptive transfer experiments, p110deltaD910A/D910A T cells failed to protect against experimental colitis. The identification of p110delta as an intracellular signaling protein that regulates the activity of CD4+CD25+Foxp3+ Tregs may facilitate the further elucidation of the molecular mechanisms responsible for Treg-mediated suppression.
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