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

Nature immunology | 2009

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

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Associated grants

  • Agency: NIAID NIH HHS, United States
    Id: T32 AI007244-26
  • Agency: Wellcome Trust, United Kingdom
    Id: GR076558MA
  • Agency: NIGMS NIH HHS, United States
    Id: R01 GM048002-14
  • Agency: NIGMS NIH HHS, United States
    Id: R01 GM048002-15
  • Agency: NIAID NIH HHS, United States
    Id: R56 AI073870
  • Agency: NIAID NIH HHS, United States
    Id: T32 AI07244
  • Agency: NIGMS NIH HHS, United States
    Id: R01 GM048002-13A1
  • Agency: NIGMS NIH HHS, United States
    Id: R01 GM048002-16
  • Agency: NIGMS NIH HHS, United States
    Id: R01 GM048002
  • Agency: NIAID NIH HHS, United States
    Id: AI073870
  • Agency: NIAID NIH HHS, United States
    Id: R01 AI073870
  • Agency: NIAID NIH HHS, United States
    Id: R01 AI073870-01A2
  • Agency: NIAID NIH HHS, United States
    Id: T32 AI007244
  • Agency: NIGMS NIH HHS, United States
    Id: GM048002

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laboratory mouse with name 129/SvEv from MGI.

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