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dc.contributor.authorMILLS, KINGSTON
dc.date.accessioned2009-09-28T18:37:52Z
dc.date.available2009-09-28T18:37:52Z
dc.date.issued1998
dc.date.submitted1998en
dc.identifier.citationRyan, M. McCarthy, L., Mahon, B, Rappuoli, R. Mills K.H.G. `Pertussis Toxin potentiates Th1 and Th2 responses to co-injected antigen: adjuvant action is associated with enhanced regulatory cytokine production and expression of the co-stimulatory molecules B7-1, B7-2 and CD28? in International Immunology, 10, (4), 1998, pp 651 - 662en
dc.identifier.otherY
dc.identifier.otherYen
dc.identifier.urihttp://hdl.handle.net/2262/33373
dc.descriptionPUBLISHEDen
dc.description.abstractPertussis toxin (PT) is a major virulence factor of Bordetella pertussis which exerts a range of effects on the immune system, including the enhancement of IgE, IgA and IgG production, delayed-type hypersensitivity reactions, and the induction of experimental autoimmune diseases. However, the mechanism by which PT mediates adjuvanticity remains to be defined. In this investigation we have shown that PT can potentiate antigen-specific T cell proliferation and the secretion of IFN-gamma, IL-2, IL-4 and IL-5 when injected with foreign antigens. A chemically detoxified PT and a genetic mutant with substitutions/deletions in the S-1 and B oligomer components that abrogate enzymatic and binding activity displayed no adjuvant properties. In contrast, a non-toxic S-1 mutant devoid of enzymatic activity but still capable of receptor binding retained its adjuvanticity, augmenting the activation of both Th1 and Th2 subpopulations of T cells. In an attempt to address the mechanism of T cell activation, we found that PT stimulated the production of IFN-gamma and IL-2 by naive T cells and IL-1 by macrophages. Therefore potentiation of distinct T cell subpopulations may have resulted in part from the positive influence of IFN-gamma on the development of Th1 cells and the co-stimulatory role of IL-1 for Th2 cells. Furthermore, PT augmented expression of the co-stimulatory molecules B7-1 and B7-2 on macrophages and B cells, and CD28 on T cells, suggesting that the adjuvant effect may also be associated with facilitation of the second signal required for maximal T cell activation. This study demonstrates that the immunopotentiating properties of PT are largely independent of ADP-ribosyltransferase activity, but are dependent on receptor binding activity and appear to involve enhanced activation of T cells.en
dc.description.sponsorshipThis work was supported by grants from the Wellcome Trust (grant no. 039583) and the Irish Health Research Board.en
dc.format.extent651en
dc.format.extent662en
dc.format.extent536524 bytes
dc.format.mimetypeapplication/pdf
dc.language.isoenen
dc.publisherOxford University Pressen
dc.relation.ispartofseriesInternational Immunologyen
dc.relation.ispartofseries10en
dc.relation.ispartofseries4en
dc.rightsYen
dc.subjectBiochemistryen
dc.titlePertussis Toxin potentiates Th1 and Th2 responses to co-injected antigen: adjuvant action is associated with enhanced regulatory cytokine production and expression of the co-stimulatory molecules B7-1, B7-2 and CD28en
dc.typeJournal Articleen
dc.contributor.sponsorHealth Research Board
dc.contributor.sponsorWellcome Trust
dc.type.supercollectionscholarly_publicationsen
dc.type.supercollectionrefereed_publicationsen
dc.identifier.peoplefinderurlhttp://people.tcd.ie/millsk
dc.identifier.rssinternalid7726


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