title: The transmembrane adapter protein SIT regulates thymic development and peripheral T-cell functions.
abstract: 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.
authors.affiliation: Otto von Guericke University, Institute of Immunology, Magdeburg, Germany. luca.simeoni@medizin.uni-magdeburg.de
authors.forename: Luca
authors.initials: L
authors.lastname: Simeoni
authors.forename: Vilmos
authors.initials: V
authors.lastname: Posevitz
authors.forename: Uwe
authors.initials: U
authors.lastname: Kölsch
authors.forename: Ines
authors.initials: I
authors.lastname: Meinert
authors.forename: Eddy
authors.initials: E
authors.lastname: Bruyns
authors.forename: Klaus
authors.initials: K
authors.lastname: Pfeffer
authors.forename: Dirk
authors.initials: D
authors.lastname: Reinhold
authors.forename: Burkhart
authors.initials: B
authors.lastname: Schraven
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D001402:B-Lymphocytes / Q000166:cytology / Q000378:metabolism; D002454:Cell Differentiation; D008198:Lymph Nodes / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D008565:Membrane Proteins / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008822:Mice, Transgenic; D011948:Receptors, Antigen, T-Cell / Q000378:metabolism; D013601:T-Lymphocytes / Q000166:cytology* / Q000276:immunology / Q000378:metabolism*; D013950:Thymus Gland / Q000166:cytology* / Q000276:immunology / Q000378:metabolism; D015854:Up-Regulation
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D008565:Membrane Proteins; D011948:Receptors, Antigen, T-Cell; C503874:SIT protein, mouse