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

Journal article

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.

Authors: Fu, G; Vallée, S; Rybakin, V; McGuire, M; Ampudia, J

• Publication status: Published
• Journal: Nature immunology
• Volume: 10
• Issue: 8
• Pages: 848-856
• Publication date: 2009-08-01
• DOI: 10.1038/ni.1766
• EISSN: 1529-2916
• ISSN: 1529-2908
• Language: English
• Keywords: Oligonucleotide Array Sequence Analysis; Cell Differentiation; Organ Specificity; Female; Humans; Proteins; Amino Acid Sequence; Cell Survival; Mice; Signal Transduction; Animals; Cell Lineage; Flow Cytometry; Receptors, Antigen, T-Cell; Molecular Sequence Data; Cloning, Molecular; Mice, Knockout; CD4-Positive T-Lymphocytes; Cells, Cultured; CD8-Positive T-Lymphocytes