Themis controls thymocyte selection through regulation of T cell antigen receptor-mediated signaling

被引：121

作者：

Fu, Guo ^{[1
]}

Vallee, Sebastien ^{[1
]}

Rybakin, Vasily ^{[1
]}

McGuire, Marielena V. ^{[1
]}

Ampudia, Jeanette ^{[1
]}

Brockmeyer, Claudia ^{[2
]}

Salek, Mogjiborahman ^{[2
]}

Fallen, Paul R. ^{[1
]}

Hoerter, John A. H. ^{[1
]}

Munshi, Anil ^{[1
]}

Huang, Yina H. ^{[1
]}

Hu, Jianfang ^{[1
]}

Fox, Howard S. ^{[3
]}

Sauer, Karsten ^{[1
]}

Acuto, Oreste ^{[2
]}

Gascoigne, Nicholas R. J. ^{[1
]}

机构：

[1] Scripps Res Inst, Dept Immunol & Microbial Sci, La Jolla, CA 92037 USA

[2] Univ Oxford, Sir William Dunn Sch Pathol, T Cell Signalling Lab, Oxford OX1 3RE, England

[3] Scripps Res Inst, Dept Mol & Integrat Neurosci, La Jolla, CA 92037 USA

来源：

NATURE IMMUNOLOGY | 2009年 / 10卷 / 08期

基金：

英国惠康基金; 美国国家卫生研究院;

关键词：

THYMIC POSITIVE SELECTION; TRANSGENIC MICE; LYMPHOCYTE DEVELOPMENT; NEGATIVE SELECTION; ALLELIC EXCLUSION; FAMILY KINASES; IMMUNE-SYSTEM; IN-VIVO; ACTIVATION; DIFFERENTIATION;

D O I：

10.1038/ni.1766

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

071005 [微生物学]; 100108 [医学免疫学];

摘要：

Themis (thymocyte-expressed molecule involved in selection), a member of a family of proteins with unknown functions, is highly conserved among vertebrates. Here we found that Themis had high expression in thymocytes between the pre-T cell antigen receptor (pre-TCR) and positive-selection checkpoints and low expression in mature T cells. Themis-deficient thymocytes showed defective positive selection, which resulted in fewer mature thymocytes. Negative selection was also impaired in Themis-deficient mice. A greater percentage of Themis-deficient T cells had CD4(+)CD25(+)Foxp3(+) regulatory and CD62L(lo)CD44(hi) memory phenotypes than did wild-type T cells. In support of the idea that Themis is involved in TCR signaling, this protein was phosphorylated quickly after TCR stimulation and was needed for optimal TCR-driven calcium mobilization and activation of the kinase Erk.

引用

页码：848 / U71

页数：10

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