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

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 NFκB 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 TNFα 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 TNFα 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. pig / dendritic cell / cholera toxin / adjuvant

Varying Effects of Different β-Glucans on the Maturation of Porcine Monocyte-Derived Dendritic Cells

“…Although intestinal DCs are presumed to be the in vivo target for ␤-glucan activity, they are not easily accessible for in vitro studies. In contrast, MoDCs are a well-established DC model in swine research (3,25). The results of the present study demonstrate that there is a large variation in terms of DC maturation-inducing properties between the different ␤-glucans.…”

Aflatoxins of type B and G affect porcine dendritic cell maturationin vitro

“…after the treatment period these wells were then pooled to collect the MoDC for staining). These assays were performed using mAb against MHC-II (MSA3, IgG 2a ; Lunney et al, 1994), CD40 (G28-5, IgG 1 , anti-human; Bimczok et al, 2007), CD25 (K231.3B2, IgG 1 ; Bailey et al, 1992), and a human CTLA4-muIgG 2a fusion protein (all from Ancell, Bayport, MN), respectively, followed by R-phycoerythrin-and AlexaFluor-647-conjugated isotype-specific anti-mouse secondary antibodies (Life Technologies, Merelbeke, Belgium).…”

Therapeutic potential of semi-mature dendritic cells for tolerance induction

“…There is accumulating evidence that typical Th2-inducing pathogens also induce only partial DC maturation such as shown for Leishmania amazonensis (Prina et al, 2004), Bordetella pertussis (Vojtova et al, 2006), cholera toxin (Bimczok et al, 2007), Nippostrongylus brasiliensis (Balic et al, 2004), or Echinococcus multilocularis (Nono et al, 2012). As a consequence the resulting Th2 response will be dominated by Tr1 cells due to the chronicity of the infection (O’Garra et al, 2004) and was similar as observed for repetitive injections of TNF/DCs in the autoimmune models mentioned above.…”