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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 Summerfieldca 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
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
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
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
Corresponding author: dianebimczok@yahoo.de
© INRA, EDP Sciences 2007
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