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The transmembrane adapter protein SIT regulates thymic development and peripheral T-cell functions.

SIT is a transmembrane adapter protein that modulates signals emanating from the T-cell receptor (TCR). Here, we have used gene-targeted mice to assess the role of SIT for T-cell development and peripheral T-cell functions. SIT(-/-) double-positive thymocytes show an upregulation of the activation markers CD5 and CD69, suggesting that SIT negatively regulates TCR-mediated signals at the CD4(+) CD8(+) stage of thymic development. This assumption is further supported by the observation that in female H-Y TCR transgenic mice, positive selection is enhanced and even converted to negative selection. Similarly, mature peripheral T cells are hyperresponsive towards TCR-mediated stimuli and produce larger amounts of T-helper 1 (TH1) cytokines, and SIT-deficient mice show an increased susceptibility to develop experimental autoimmune encephalomyelitis, a mouse model of multiple sclerosis. These results demonstrate that SIT is a critical negative regulator of TCR-mediated signaling and finely tunes the signals required for thymic selection and peripheral T-cell activation.

Pubmed ID: 16107703


  • Simeoni L
  • Posevitz V
  • K├Âlsch U
  • Meinert I
  • Bruyns E
  • Pfeffer K
  • Reinhold D
  • Schraven B


Molecular and cellular biology

Publication Data

September 18, 2005

Associated Grants


Mesh Terms

  • Adaptor Proteins, Signal Transducing
  • Animals
  • B-Lymphocytes
  • Cell Differentiation
  • Lymph Nodes
  • Membrane Proteins
  • Mice
  • Mice, Transgenic
  • Receptors, Antigen, T-Cell
  • T-Lymphocytes
  • Thymus Gland
  • Up-Regulation