title: OdDHL inhibits T cell subset differentiation and delays diabetes onset in NOD mice.
abstract: Some infectious diseases have been shown to halt the onset of autoimmune disease in animal models and have been suggested to also influence autoimmune pathology in humans. The isolation and study of small molecules and proteins from the infectious agents responsible for the protective effect will enable a mechanistic understanding of how these components may prevent or delay the onset of autoimmunity. In this study we confirm that the quorum-sensing signal molecule OdDHL from Pseudomonas aeruginosa can delay the onset of type 1 diabetes in the NOD mouse model. Furthermore, using an antigen-presenting cell-free system, we find not only that OdDHL inhibits the proliferation of naïve T cells but also that it directly inhibits the differentiation of T cell subsets. OdDHL was shown to have no effect on the inhibition of primed and committed differentiated T cell responses, suggesting that that immune mechanism mediated by this molecule may be more restricted to initial stages of infection.
authors.affiliation: Department of Pathology, University of Cambridge, Tennis Court Road, Cambridge CB2 1QP, United Kingdom.
authors.forename: Wendy
authors.initials: W
authors.lastname: Gaisford
authors.forename: David I
authors.initials: DI
authors.lastname: Pritchard
authors.forename: Anne
authors.initials: A
authors.lastname: Cooke
mesh_terms: D015107:4-Butyrolactone / Q000031:analogs & derivatives* / Q000378:metabolism; D000818:Animals; D001327:Autoimmune Diseases / Q000276:immunology / Q000517:prevention & control; D002454:Cell Differentiation / Q000187:drug effects*; D049109:Cell Proliferation / Q000187:drug effects; D003922:Diabetes Mellitus, Type 1 / Q000276:immunology* / Q000517:prevention & control*; D006714:Homoserine / Q000031:analogs & derivatives* / Q000378:metabolism; D007155:Immunologic Factors / Q000378:metabolism*; D051379:Mice; D016688:Mice, Inbred NOD; D011550:Pseudomonas aeruginosa / Q000378:metabolism*; D016176:T-Lymphocyte Subsets / Q000276:immunology*
chemical_list: D007155:Immunologic Factors; C109860:N-(3-oxododecanoyl)homoserine lactone; D006714:Homoserine; D015107:4-Butyrolactone