Cutting edge: T cell development requires the combined activities of the p110gamma and p110delta catalytic isoforms of phosphatidylinositol 3-kinase.
J Immunol
; 175(5): 2783-7, 2005 Sep 01.
Article
em En
| MEDLINE
| ID: mdl-16116162
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.
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Base de dados:
MEDLINE
Assunto principal:
Linfócitos T
/
Fosfatidilinositol 3-Quinases
Limite:
Animals
Idioma:
En
Ano de publicação:
2005
Tipo de documento:
Article