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 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.
Hoyne
G F
GF
Respiratory Medicine Unit, University of Edinburgh Medical School, Teviot Place, Edinburgh EH8 9AG, UK.
Le Roux
I
I
Corsin-Jimenez
M
M
Tan
K
K
Dunne
J
J
Forsyth
L M
LM
Dallman
M J
MJ
Owen
M J
MJ
Ish-Horowicz
D
D
Lamb
J R
JR
D000818:Animals; D000938:Antigen-Presenting Cells / Q000276:immunology / Q000378:metabolism; D039741:Antigens, Dermatophagoides; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D002135:Calcium-Binding Proteins; D002478:Cells, Cultured; D000939:Epitopes / Q000276:immunology; D005260:Female; D005786:Gene Expression Regulation / Q000276:immunology; D006023:Glycoproteins / Q000276:immunology; D006801:Humans; D007108:Immune Tolerance; D007111:Immunity, Cellular; D007114:Immunization; D036341:Intercellular Signaling Peptides and Proteins; D000072100:Jagged-1 Protein; D007963:Leukocytes, Mononuclear / Q000276:immunology; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D010047:Ovalbumin / Q000276:immunology; D051381:Rats; D051880:Receptors, Notch; D020133:Reverse Transcriptase Polymerase Chain Reaction; D000072099:Serrate-Jagged Proteins; D015398:Signal Transduction
D039741:Antigens, Dermatophagoides; D002135:Calcium-Binding Proteins; D000939:Epitopes; D006023:Glycoproteins; D036341:Intercellular Signaling Peptides and Proteins; C000606273:JAG1 protein, human; C000606274:Jag1 protein, mouse; C000606275:Jag1 protein, rat; D000072100:Jagged-1 Protein; D008565:Membrane Proteins; D051880:Receptors, Notch; D000072099:Serrate-Jagged Proteins; D010047:Ovalbumin