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Publication : Notch1 regulates maturation of CD4+ and CD8+ thymocytes by modulating TCR signal strength.

First Author  Izon DJ Year  2001
Journal  Immunity Volume  14
Issue  3 Pages  253-64
PubMed ID  11290335 Mgi Jnum  J:68348
Mgi Id  MGI:1932593 Doi  10.1016/s1074-7613(01)00107-8
Citation  Izon DJ, et al. (2001) Notch1 regulates maturation of CD4+ and CD8+ thymocytes by modulating TCR signal strength. Immunity 14(3):253-64
abstractText  Notch signaling regulates cell fate decisions in multiple lineages. We demonstrate in this report that retroviral expression of activated Notch1 in mouse thymocytes abrogates differentiation of immature CD4+CD8+ thymocytes into both CD4 and CD8 mature single-positive T cells. The ability of Notch1 to inhibit T cell development was observed in vitro and in vivo with both normal and TCR transgenic thymocytes. Notch1-mediated developmental arrest was dose dependent and was associated with impaired thymocyte responses to TCR stimulation. Notch1 also inhibited TCR-mediated signaling in Jurkat T cells. These data indicate that constitutively active Notch1 abrogates CD4+ and CD8+ maturation by interfering with TCR signal strength and provide an explanation for the physiological regulation of Notch expression during thymocyte development.
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