Cutting edge: an essential role for Notch-1 in the development of both thymus-independent and -dependent T cells in the gut
Whereas most T cells arise in the thymus, a distinct lineage of extrathymically derived T cells is present in the gut mucosa. The developmental origin of extrathymic T cells is poorly understood. We show here that Notch-1, a transmembrane receptor involved in T cell fate specification of bipotential T/B precursors in the thymus, is absolutely required for the development of extrathymic (as well as thymus-derived) mature T cells in the intestinal epithelium. In the absence of Notch-1, CD117(+) T cell precursors are relatively more abundant in the gut than the thymus, whereas immature B cells accumulate in the thymus but not the gut. Collectively, these data demonstrate that Notch-1 is essential for both thymic and extrathymic T cell fate specification and further suggest that bipotential T/B precursors that do not receive a Notch-1 signal adopt a B cell fate in the thymus but become developmentally arrested in the gut.
- URL: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=11067889
Keywords: Animals ; Antigens ; T-Independent/*immunology ; Bone Marrow Transplantation ; CD8-Positive T-Lymphocytes/cytology/immunology/metabolism ; Cell Differentiation/genetics/immunology ; Cell Lineage/genetics/immunology ; Dimerization ; Intestinal Mucosa/*cytology/*immunology/metabolism ; Membrane Proteins/deficiency/genetics/*physiology ; Mice ; Mice ; Inbred C57BL ; Mice ; Transgenic ; Proto-Oncogene Proteins c-kit/biosynthesis ; Radiation Chimera/immunology ; Receptor ; Notch1 ; *Receptors ; Cell Surface ; Research Support ; Non-U.S. Gov't ; Signal Transduction/genetics/immunology ; T-Lymphocyte Subsets/*cytology/immunology/metabolism ; Thymus Gland/cytology/*immunology ; *Transcription Factors
Ludwig Institute for Cancer Research, Lausanne Branch, University of Lausanne, Epalinges, Switzerland.
Record created on 2006-12-05, modified on 2016-08-08