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

Nature immunology | Aug 21, 2009

http://www.ncbi.nlm.nih.gov/pubmed/19597499

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.

Pubmed ID: 19597499 RIS Download

Mesh terms: Amino Acid Sequence | Animals | CD4-Positive T-Lymphocytes | CD8-Positive T-Lymphocytes | Cell Differentiation | Cell Lineage | Cell Survival | Cells, Cultured | Cloning, Molecular | Female | Flow Cytometry | Humans | Mice | Mice, Knockout | Molecular Sequence Data | Oligonucleotide Array Sequence Analysis | Organ Specificity | Proteins | Receptors, Antigen, T-Cell | Signal Transduction

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Associated grants

  • Agency: NIAID NIH HHS, Id: AI073870
  • Agency: NIGMS NIH HHS, Id: GM048002
  • Agency: Wellcome Trust, Id: GR076558MA
  • Agency: NIAID NIH HHS, Id: R01 AI073870
  • Agency: NIAID NIH HHS, Id: R01 AI073870-01A2
  • Agency: NIGMS NIH HHS, Id: R01 GM048002
  • Agency: NIGMS NIH HHS, Id: R01 GM048002-13A1
  • Agency: NIGMS NIH HHS, Id: R01 GM048002-14
  • Agency: NIGMS NIH HHS, Id: R01 GM048002-15
  • Agency: NIGMS NIH HHS, Id: R01 GM048002-16
  • Agency: NIAID NIH HHS, Id: T32 AI007244-26
  • Agency: NIAID NIH HHS, Id: T32 AI07244

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