PMID:12707323

Citation	Rodríguez-Borlado, L, Barber, DF, Hernández, C, Rodríguez-Marcos, MA, Sánchez, A, Hirsch, E, Wymann, M, Martínez-A, C and Carrera, AC (2003) Phosphatidylinositol 3-kinase regulates the CD4/CD8 T cell differentiation ratio. J. Immunol. 170:4475-82
Abstract	The signaling pathways that control T cell differentiation have only begun to be elucidated. Using T cell lines, it has been shown that class IA phosphatidylinositol 3-kinase (PI3K), a heterodimer composed of a p85 regulatory and a p110 catalytic subunit, is activated after TCR stimulation. Nonetheless, the contribution of p85/p110 PI3K isoforms in T cell development has not been described. Mice deficient in the other family of class I PI3K, p110gamma, which is regulated by G protein-coupled receptors, exhibit reduced thymus size. Here we examine T cell development in p110gamma-deficient mice and in mice expressing an activating mutation of the p85 regulatory subunit, p65(PI3K), in T cells. We show that p110gamma-deficient mice have a partial defect in pre-TCR-dependent differentiation, which is restored after expression of the p65(PI3K) activating mutation. Genetic alteration of both PI3K isoforms also affects positive selection; p110gamma deletion decreased and p65(PI3K) expression augmented the CD4(+)/CD8(+) differentiation ratio. Finally, data are presented showing that both PI3K isoforms influenced mature thymocyte migration to the periphery. These observations underscore the contribution of PI3K in T cell development, as well as its implication in determining the CD4(+)/CD8(+) T cell differentiation ratio in vivo.
Links	PubMed
Keywords	Animals; Antigens, CD4/biosynthesis; Antigens, CD8/biosynthesis; CD4-CD8 Ratio; CD4-Positive T-Lymphocytes/cytology; CD4-Positive T-Lymphocytes/enzymology; CD4-Positive T-Lymphocytes/immunology; CD4-Positive T-Lymphocytes/metabolism; CD8-Positive T-Lymphocytes/cytology; CD8-Positive T-Lymphocytes/enzymology; CD8-Positive T-Lymphocytes/immunology; CD8-Positive T-Lymphocytes/metabolism; Cell Differentiation/genetics; Cell Differentiation/immunology; Down-Regulation/genetics; Down-Regulation/immunology; Enzyme Activation/genetics; Enzyme Activation/immunology; Female; Histocompatibility Antigens Class II/genetics; Isoenzymes/metabolism; Isoenzymes/physiology; Mice; Mice, Inbred C57BL; Mice, Knockout; Mice, Transgenic; Phosphatidylinositol 3-Kinases/deficiency; Phosphatidylinositol 3-Kinases/genetics; Phosphatidylinositol 3-Kinases/metabolism; Phosphatidylinositol 3-Kinases/physiology; Receptors, Antigen, T-Cell/genetics; Transgenes/immunology
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Annotations

Gene product	Qualifier	GO Term	Evidence Code	with/from	Aspect	Extension	Notes	Status
MOUSE:PI3R6		GO:0045582: positive regulation of T cell differentiation	ECO:0000315:		P		Figure 2. Enhanced class IA PI3K activation increases CD4+ T cell generation.	complete CACAO 6519
MOUSE:PI3R6	involved_in	GO:0045582: positive regulation of T cell differentiation	ECO:0000315: mutant phenotype evidence used in manual assertion		P		Seeded From UniProt	complete

References

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