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    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


    Ryan, Mark and McCarthy, Leone and Rappuoli, Rino and Mahon, Bernard P. and Mills, Kingston H.G. (1998) 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. International Immunology, 10 (4). pp. 651-662. ISSN 0953-8178

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    Abstract

    Pertussis 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, delayedtype 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-g, 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-g 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-g on the development of Th1 cells and the costimulatory 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.

    Item Type: Article
    Additional Information: We are grateful to Michel Aguet for permission to use the IFN-gR–/– mice, Yves Lobet and Carine Capiau for the mutant toxin PTX-RENK, Steve Poole for anti-IL-1 antibody, and to Luke O’Neill for providing the IL-1ra and for helpful discussions. This work was supported by grants from the Wellcome Trust (grant no. 039583) and the Irish Health Research Board.
    Keywords: Pertussis toxin; potentiates; Th1; Th2; co-injected antigen; cytokine production; co-stimulatory molecules; B7-1; B7-2; CD28;
    Academic Unit: Faculty of Science and Engineering > Biology
    Item ID: 7162
    Identification Number: https://doi.org/10.1093/intimm/10.5.651
    Depositing User: Bernard Mahon
    Date Deposited: 05 Jul 2016 15:48
    Journal or Publication Title: International Immunology
    Publisher: Oxford University Press
    Refereed: Yes
    Funders: Wellcome Trust, Health Research Board (HRB)
    URI:

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