Cholera toxin promotes the generation of semi-mature porcine monocyte-derived dendritic cells that are unable to stimulate T cells.
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 NFkappaB 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 TNFalpha 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 TNFalpha 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.
Bimczok
Diane
D
Institute of Anatomy, Otto-von-Guericke University Magdeburg, Leipziger Strasse 44, 39120 Magdeburg, Germany. dianebimczok@yahoo.de
Rau
Henriette
H
Wundrack
Nicole
N
Naumann
Michael
M
Rothkötter
Hermann-Josef
HJ
McCullough
Kenneth
K
Summerfield
Artur
A
D000818:Animals; D017209:Apoptosis; D015415:Biomarkers; D002454:Cell Differentiation / Q000187:drug effects*; D049109:Cell Proliferation; D002478:Cells, Cultured; D002772:Cholera Toxin / Q000494:pharmacology*; D003713:Dendritic Cells / Q000166:cytology* / Q000187:drug effects* / Q000276:immunology; D048049:Extracellular Signal-Regulated MAP Kinases / Q000235:genetics / Q000378:metabolism; D005786:Gene Expression Regulation; D016753:Interleukin-10 / Q000235:genetics / Q000378:metabolism; D009000:Monocytes / Q000166:cytology*; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism; D013552:Swine; D013601:T-Lymphocytes / Q000166:cytology* / Q000187:drug effects / Q000276:immunology; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000378:metabolism
D015415:Biomarkers; D016328:NF-kappa B; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D002772:Cholera Toxin; D048049:Extracellular Signal-Regulated MAP Kinases