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Vet. Res.
Volume 38, Number 4, July-August 2007
Page(s) 597 - 612
Published online 13 June 2007
How to cite this article Vet. Res. (2007) 597-612
Vet. Res. 38 (2007) 597-612
DOI: 10.1051/vetres:2007020

Cholera toxin promotes the generation of semi-mature porcine monocyte-derived dendritic cells that are unable to stimulate T cells

Diane Bimczoka, Henriette Raua, Nicole Wundrackb, Michael Naumannb, Hermann-Josef Rothköttera, Kenneth McCulloughc and Artur Summerfieldc

a  Institute of Anatomy, Otto-von-Guericke University Magdeburg, Leipziger Strasse 44, 39120 Magdeburg, Germany
b  Institute of Experimental Internal Mediane, Otto-von-Guiricke University, Magdeburg, Germany
c  Institute of Virology and Immunoprophylaxis (IVI), Mittelhäusenn, Switzerland

(Received 11 October 2006; accepted 16 February 2007 ; published online 13 June 2007)

Abstract - Cholera toxin (Ctx) is a powerful mucosal adjuvant with potential applications for oral vaccination of swine. Dendritic cells (DC) play a key role in the decision between immunity and tolerance, and are likely target cells for mediating Ctx functions in vivo. Therefore, we examined the capacity of Ctx to enhance stimulatory activity of porcine monocyte-derived DC (MoDC). Ctx promoted the development of a semi-mature DC phenotype, with decreased levels of MHC class II and CD40, but increased CD80/86 expression. These changes were associated with activation of extracellular signal-regulated kinase (ERK), but not NF${\kappa}$B or c-Jun N-terminal kinase (JNK). Functionally, Ctx-priming greatly diminished T cell stimulatory capacity both in antigen-specific and superantigen-induced proliferation assays. The lower proliferation rate was not due to increased apoptosis of either DC or T cells. Ctx suppressed TNF${\alpha} $ secretion by MoDC, but induced IL-10 production. The observed effects on T cell proliferation could only be partially mimicked by IL-10 alone. However, addition of recombinant TNF${\alpha} $ to co-cultures of Ctx-primed MoDC and lymphocytes restored lymphocyte proliferation in a concentration-dependent manner. Ctx-primed DC were not actively tolerogenic, since they could not suppress proliferative T cell reactions induced by untreated DC.

Key words: pig / dendritic cell / cholera toxin / adjuvant

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© INRA, EDP Sciences 2007