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Altered development of CD8+ T cell lineages in mice deficient for the Tec kinases Itk and Rlk.

Abstract：

:Mutations affecting the Tec kinases Itk and Rlk decrease T cell receptor-induced Ca(2+) mobilization and Erk kinase activation and impair both positive and negative thymic selection. Itk(-/-) and Rlk(-/-)Itk(-/-) mice also have decreased CD4:8 T cell ratios, suggestive of altered CD4:8 lineage commitment. Nonetheless, we find that CD8 single-positive (SP) thymocytes and peripheral CD8(+) T cells in these mice do not resemble conventional CD8(+) T cells. Instead, these cells express memory markers, rapidly produce interferon-gamma, and can be selected on hematopoietically derived cells, similar to MHC class Ib-restricted "innate-type" lymphocytes. Itk deficiency also greatly increases the number of cells selected by MHC class Ib. Expression of a hypersensitive Erk2 mutant partially corrects the CD8(+) T cell phenotypes in Itk(-/-) mice, arguing that altered signaling permits development of this innate-type CD8(+) cell population. Our results suggest that Tec kinases differentially regulate development of conventional versus nonconventional lymphocytes.

journal_name

Immunity

journal_title

Immunity

authors

Broussard C,Fleischacker C,Horai R,Chetana M,Venegas AM,Sharp LL,Hedrick SM,Fowlkes BJ,Schwartzberg PL

doi

10.1016/j.immuni.2006.05.011

subject

Has Abstract

pub_date

2006-07-01 00:00:00

pages

93-104

issue

1

eissn

1074-7613

issn

1097-4180

pii

S1074-7613(06)00306-2

journal_volume

25

pub_type

杂志文章

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