Format

Send to

Choose Destination
Immunity. 2001 Mar;14(3):253-64.

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

Author information

1
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.

PMID:
11290335
DOI:
10.1016/s1074-7613(01)00107-8
[Indexed for MEDLINE]
Free full text

Publication types, MeSH terms, Substances

Publication types

MeSH terms

Substances

Supplemental Content

Full text links

Icon for Elsevier Science
Loading ...
Support Center