The transmembrane adapter protein SIT regulates thymic development and peripheral T-cell functions.
Mol Cell Biol
; 25(17): 7557-68, 2005 Sep.
Article
em En
| MEDLINE
| ID: mdl-16107703
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.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Timo
/
Linfócitos T
/
Diferenciação Celular
/
Proteínas Adaptadoras de Transdução de Sinal
/
Proteínas de Membrana
Limite:
Animals
Idioma:
En
Revista:
Mol Cell Biol
Ano de publicação:
2005
Tipo de documento:
Article
País de afiliação:
Alemanha