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Molecular and Cellular Biology, September 2005, p. 7557-7568, Vol. 25, No. 17
0270-7306/05/$08.00+0     doi:10.1128/MCB.25.17.7557-7568.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

The Transmembrane Adapter Protein SIT Regulates Thymic Development and Peripheral T-Cell Functions

Luca Simeoni,1* Vilmos Posevitz,1 Uwe Kölsch,1 Ines Meinert,1 Eddy Bruyns,2 Klaus Pfeffer,3 Dirk Reinhold,1 and Burkhart Schraven1

Otto von Guericke University, Institute of Immunology, Leipziger Str. 44, 39120 Magdeburg, Germany,1 FOCUS Clinical Drug Development GmbH, Im Neuenheimer Feld 515, 69120 Heidelberg, Germany,2 Heinrich Heine University, Institute of Medical Microbiology, Universitäts Str. 1, 40225 Düsseldorf, Germany3

Received 21 December 2004/ Returned for modification 15 February 2005/ Accepted 25 May 2005

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.

* Corresponding author. Mailing address: Otto von Guericke University, Institute of Immunology, Leipziger Strasse 44, 39120 Magdeburg, Germany. Phone: 49 391 67 17894. Fax: 49 391 6715852. E-mail: luca.simeoni{at}medizin.uni-magdeburg.de.

Molecular and Cellular Biology, September 2005, p. 7557-7568, Vol. 25, No. 17
0022-538X/05/$08.00+0     doi:10.1128/MCB.25.17.7557-7568.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

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