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Themis, a T cell-specific protein important for late thymocyte development.

During positive selection, thymocytes transition through a stage during which T cell antigen receptor (TCR) signaling controls CD4-versus-CD8 lineage 'choice' and subsequent maturation. Here we describe a previously unknown T cell-specific protein, Themis, that serves a distinct function during this stage. In Themis(-/-) mice, thymocyte selection was impaired and the number of transitional CD4(+)CD8(int) thymocytes as well as CD4(+) or CD8(+) single-positive thymocytes was lower. Notably, although we detected no overt TCR-proximal signaling deficiencies, Themis(-/-) CD4(+)CD8(int) thymocytes showed developmental defects consistent with attenuated signaling that were reversible by TCR stimulation. Our results identify Themis as a critical component of the T cell developmental program and suggest that Themis functions to sustain and/or integrate signals required for proper lineage commitment and maturation.

Pubmed ID: 19597498

Authors

  • Lesourne R
  • Uehara S
  • Lee J
  • Song KD
  • Li L
  • Pinkhasov J
  • Zhang Y
  • Weng NP
  • Wildt KF
  • Wang L
  • Bosselut R
  • Love PE

Journal

Nature immunology

Publication Data

August 21, 2009

Associated Grants

  • Agency: NIA NIH HHS, Id: Z01 AG000757-10

Mesh Terms

  • Animals
  • CD4-Positive T-Lymphocytes
  • CD8-Positive T-Lymphocytes
  • Cell Differentiation
  • Cell Lineage
  • Cell Survival
  • Cells, Cultured
  • Embryonic Stem Cells
  • Female
  • Flow Cytometry
  • Humans
  • Mice
  • Mice, Knockout
  • Oligonucleotide Array Sequence Analysis
  • Proteins
  • Receptors, Antigen, T-Cell
  • Signal Transduction