The role of PI3K activity in T lymphocyte development is obscure because mice deficient in single PI3K catalytic subunits either die before birth (p110alpha-/- and p110beta-/-) or lack a significant T cell developmental phenotype (p110gamma-/- and p110delta-/-). We have generated mice deficient in both p110gamma and p110delta and show that p110gamma/delta-/- mice have a profound block in T cell development that occurs at the beta-selection checkpoint. We show that pre-TCR-induced signaling is significantly reduced in p110gamma/delta-/- thymocytes and that this results in a concomitant lack of proliferative expansion and increased apoptosis. The survival defect in p110gamma/delta-/- thymocytes is associated with increased levels of the pro-apoptotic molecule Bcl2 interacting mediator of cell death. This work demonstrates that PI3K activity is critical for T cell development and depends on the combined function of p110gamma and p110delta.

Cutting edge: T cell development requires the combined activities of the p110gamma and p110delta catalytic isoforms of phosphatidylinositol 3-kinase.

HIRSCH, Emilio;
2005

Abstract

The role of PI3K activity in T lymphocyte development is obscure because mice deficient in single PI3K catalytic subunits either die before birth (p110alpha-/- and p110beta-/-) or lack a significant T cell developmental phenotype (p110gamma-/- and p110delta-/-). We have generated mice deficient in both p110gamma and p110delta and show that p110gamma/delta-/- mice have a profound block in T cell development that occurs at the beta-selection checkpoint. We show that pre-TCR-induced signaling is significantly reduced in p110gamma/delta-/- thymocytes and that this results in a concomitant lack of proliferative expansion and increased apoptosis. The survival defect in p110gamma/delta-/- thymocytes is associated with increased levels of the pro-apoptotic molecule Bcl2 interacting mediator of cell death. This work demonstrates that PI3K activity is critical for T cell development and depends on the combined function of p110gamma and p110delta.
175(5)
2783
2787
http://www.jimmunol.org/cgi/reprint/175/5/2783
PI3K; T cell; genetically modified mice
WEBB LM; VIGORITO E; WYMANN MP; HIRSCH E; TURNER M
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2318/40988
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