Notch1 regulates maturation of CD4+ and CD8+ thymocytes by modulating TCR signal strength |
| |
Authors: | Izon D J Punt J A Xu L Karnell F G Allman D Myung P S Boerth N J Pui J C Koretzky G A Pear W S |
| |
Affiliation: | Department of Pathology and Laboratory Medicine, University of Pennsylvania Medical Center, Philadelphia, PA 19104, USA. |
| |
Abstract: | 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. |
| |
Keywords: | |
本文献已被 ScienceDirect PubMed 等数据库收录! |