Phosphatidylinositol 3-kinase regulates the CD4/CD8 T cell differentiation ratio.
نویسندگان
چکیده
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.
منابع مشابه
Effect of ionizing radiation on development process of T-cell population lymphocytes in Chernobyl children
Background: The aim of preliminary study was determined development process status of T-cell population lymphocytes in Ukrainian children after 22 years from Chernobyl accident for next feasibility study. Material and Method: 150 participants aged 6 to 16 years are included in three groups: Group I (n=65), 30 to 60 km from center accident at zone 3th, Group II (n=65) 60 to 90 km from s...
متن کاملLy6C induces clustering of LFA-1 (CD11a/CD18) and is involved in subtype-specific adhesion of CD8 T cells.
Ly6C is a hemopoietic cell differentiation Ag found on a subset of CD8 T cells in the periphery. It is involved in target cell killing by CTLs, augments TCR-mediated activation of IL-2 and IFN-gamma production in CD8 T cells, and regulates CD8 T cell homing in vivo. In this study, we show that cross-linking of Ly6C causes clustering of LFA-1 (CD11a/CD18) on the surface of CD8 T cells via a mech...
متن کاملO 1: The Effects of Vitamin D Supplementation on the T cell Compartment in Multiple Sclerosis
Multiple sclerosis (MS) is a complex neurological disease and its prevalence is about 2 million in the world. Neuroinflammation plays a key role in MS. Vitamins are essential nutrients that have effective role on immune system including activation of lymphocyte and differentiation of T-helper cell. Vitamin D is a micronutrient that is effective on immune function. Deficiently of Vitamin D is a ...
متن کاملتعیین زیر جمعیت های لنفوسیت T و B و NK بکمک آنتی بادی های مونوکلونال در بیماران مبتلا به بیماری بهجت در ایران
Behcet disease (BD) is a systemic inflammatory disease of the unknown etiology. There is however, some evidence to suggest that immunological abnormalities are important in its pathogenesis, furthermore several T-cell abnormalities which may be quite relevant to autoimmune origin of the disease have been described. We report here our study of T-cell subsets, B and NK cells in 68 patients with B...
متن کاملذخیره در منابع من
با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید
عنوان ژورنال:
- Journal of immunology
دوره 170 9 شماره
صفحات -
تاریخ انتشار 2003