Cholera toxin promotes the induction of regulatory T cells by modulation dendritic cell activation
Citation:
Lavelle, E., McNeela, E., Armstrong, M., Leavy, O., Higgins, S.C. and Mills K.H.G. `Cholera toxin promotes the induction of regulatory T cells by modulation dendritic cell activation? in The Journal of Immunology, 171, 2003, pp 2384 - 2392Download Item:
Cholera toxin promotes the induction of regulatory T cells specific for bystander antigens by modulating dendritic cell activation.pdf (published (publisher copy) peer-reviewed) 322.4Kb
Abstract:
It has previously been reported that cholera toxin (CT) is a potent mucosal adjuvant that enhances Th2 or mixed Th1/Th2 type responses to coadministered foreign Ag. Here we demonstrate that CT also promotes the generation of regulatory T (Tr) cells against bystander Ag. Parenteral immunization of mice with Ag in the presence of CT induced T cells that secreted high levels of IL-4 and IL-10 and lower levels of IL-5 and IFN-. Ag-specific CD4+ T cell lines and clones generated from these mice had cytokine profiles characteristic of Th2 or type 1 Tr cells, and these T cells suppressed IFN- production by Th1 cells. Furthermore, adoptive transfer of bone marrow-derived dendritic cells (DC) incubated with Ag and CT induced T cells that secreted IL-4 and IL-10 and low concentrations of IL-5. It has previously been shown that IL-10 promotes the differentiation or expansion of type 1 Tr cells. Here we found that CT synergized with low doses of LPS to induce IL-10 production by immature DC. CT also enhanced the expression of CD80, CD86, and OX40 (CD134) on DC and induced the secretion of the chemokine, macrophage inflammatory protein-2 (MIP-2), but inhibited LPS-driven induction of CD40 and ICAM-I expression and production of the inflammatory cytokines/chemokines IL-12, TNF-, MIP-1, MIP-1, and monocyte chemoattractant protein-1. Our findings suggest that CT induces maturation of DC, but, by inducing IL-10, inhibiting IL-12, and selectively affecting surface marker expression, suppresses the generation of Th1 cells and promotes the induction of T cells with regulatory activity.
Sponsor
Grant Number
Science Foundation Ireland
European Union (EU)
Author's Homepage:
http://people.tcd.ie/millskDescription:
PUBLISHED
Author: LAVELLE, EDWARD; MILLS, KINGSTON
Publisher:
The American Association of ImmunologistsType of material:
Journal ArticleCollections:
Series/Report no:
The Journal of Immunology171
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BiochemistryLicences: