Notch ligand-bearing thymic epithelial cells initiate and sustain Notch signaling in thymocytes independently of T cell receptor signaling

Graham Anderson, Judit Pongracz, Sonia Parnell, Eric J. Jenkinson

Research output: Article

66 Citations (Scopus)

Abstract

Thymic epithelial cells are specialized to play essential roles at multiple stages of T cell development in the thymus, yet the molecular basis of this specialization is largely unknown. Recently, the Notch family of transmembrane proteins has been implicated in thymocyte development. Such proteins interact with cell surface proteins of the Delta-like and Jagged families. It is known that Notch ligands are expressed intrathymically, and that Notch signaling is regulated by Notch ligands expressed on either the same or third-party cells. However, functional analysis of Notch ligand expression, and elucidation of the mechanism of Notch ligand signaling in thymocyte development, are unclear. Here, we find that Notch ligand expression in the thymus is compartmentalized, with MHC class II+ thymic epithelium, but not thymocytes nor dendritic cells, expressing Jagged-1, Jagged-2 and Delta-like-1. We also provide evidence that contact with Notch ligands on thymic epithelium is necessary to activate and sustain Notch signaling in thymocytes, and that this can occur independently of positive selection induction. Our data suggest that Notch ligand expression by thymic epithelium may partly explain the specialization of these cells in supporting thymocyte development, by regulating Notch activation via an inductive signaling mechanism independently of signaling leading to positive selection.

Original languageEnglish
Pages (from-to)3349-3354
Number of pages6
JournalEuropean journal of immunology
Volume31
Issue number11
DOIs
Publication statusPublished - dec. 11 2001

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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