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

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

Authors

  • Fu G
  • Vallée S
  • Rybakin V
  • McGuire MV
  • Ampudia J
  • Brockmeyer C
  • Salek M
  • Fallen PR
  • Hoerter JA
  • Munshi A
  • Huang YH
  • Hu J
  • Fox HS
  • Sauer K
  • Acuto O
  • Gascoigne NR

Journal

Nature immunology

Publication Data

August 21, 2009

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

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