International Immunology, Vol. 12, No. 2, 177-185,
February 2000
© 2000 Japanese Society for Immunology
Serrate1-induced Notch signalling regulates the decision between immunity and tolerance made by peripheral CD4+ T cells
Respiratory Medicine Unit, University of Edinburgh Medical School, Teviot Place, Edinburgh EH8 9AG, UK
1 Developmental Genetics and
2 Lymphocyte Molecular Biology Laboratories, Imperial Cancer Research Fund, Lincoln's Inn Fields, London WC2A 3PX, UK
3 Department of Biology, Imperial College of Science Technology and Medicine, Sir Alexander Fleming Building, Imperial College Road, London SW7 2AZ, UK
Correspondence to: G. F. Hoyne
Signals derived from antigen-presenting cells (APC) influence the functional differentiation of CD4+ T cells. We report here that Serrate1 (Jagged1), a ligand for the Notch1 receptor, may contribute to the differentiation of peripheral CD4+ T cells into either helper or regulatory cells. Our findings demonstrate that antigen presented by murine APC overexpressing human Serrate1 induces naive peripheral CD4+ T cells to become regulatory cells. These cells can inhibit primary and secondary immune responses, and transfer antigen-specific tolerance to recipient mice. Our results show that Notch signalling may help explain `linked' suppression in peripheral tolerance, whereby tolerance induced to one epitope encompasses all epitopes on that antigen during the course of an immune response.
Keywords: antigen-presenting cells, Notch signalling, peripheral tolerance, regulatory T cells
Transmitting editor: A. McMichael
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