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
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: |
|
| Use Licence: |
This item is available under a Creative Commons Attribution Non Commercial Share Alike Licence (CC BY-NC-SA). Details of this licence are available
here |
Repository Staff Only(login required)
 |
Item control page |
Downloads per month over past year
Origin of downloads
Altmetric
Altmetric