Serrate1-induced Notch signalling regulates the decision between immunity and tolerance made by peripheral CD4+ T cells

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 finding...

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Bibliographic Details
Published in:International immunology 2000-02, Vol.12 (2), p.177-185
Main Authors: Hoyne, Gerard F., Le Roux, Isabelle, Corsin-Jimenez, Marta, Tan, Karen, Dunne, Jenny, Forsyth, Lynn M. G., Dallman, Margaret J., Owen, Michael J., Ish-Horowicz, David, Lamb, Jonathan R.
Format: Article
Language:English
Subjects:
Animals
antigen-presenting cells
Antigen-Presenting Cells - immunology
Antigen-Presenting Cells - metabolism
Antigens, Dermatophagoides
APC antigen-presenting cell
Calcium-Binding Proteins
CD4-Positive T-Lymphocytes - immunology
Cells, Cultured
CFA complete Freund's adjuvant
DC dendritic cell
Epitopes - immunology
Female
Gene Expression Regulation - immunology
Glycoproteins - immunology
Humans
Immune Tolerance
Immunity, Cellular
Immunization
Intercellular Signaling Peptides and Proteins
Jagged-1 Protein
Leukocytes, Mononuclear - immunology
LN lymph node
Membrane Proteins - genetics
Membrane Proteins - metabolism
Mice
Notch signalling
OVA ovalbumin
Ovalbumin - immunology
peripheral tolerance
Rats
Receptors, Notch
regulatory T cells
Reverse Transcriptase Polymerase Chain Reaction
Serrate-Jagged Proteins
Signal Transduction
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Description
Summary: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.
ISSN:0953-8178
1460-2377
DOI:10.1093/intimm/12.2.177