Cholera toxin induces maturation of human dendritic cells and licences them for Th2 priming

Cholera toxin (CT) is a potent mucosal adjuvant that amplifies B and T cell responses to mucosally co-administered antigens, stimulating predominant T h2-type responses. However, little is known about the mechanism of adjuvant icity of CT and on the influence this toxin may have on Th2 cell developmen t during the priming of an immune response. We analyzed the effect of CT on dendritic cells (DC), which are responsible for the priming of immune resp onses at the systemic as well as at the mucosal level. We found that CT ind uces phenotypic and functional maturation of blood monocyte-derived DC. Ind eed, CT-treated DC up-regulate expression of HLA-DR molecules, B7.1 and B7. 2 co-stimulatory molecules, and are able to prime naive CD4(+)CD45RA(+) T c ells in vitro, driving their polarization towards the Th2 phenotype. Furthe rmore, CT-matured DC express functional chemokine receptors CCR7 and CXCR4 which may render them responsive to migratory stimuli towards secondary lym phoid organs. Interestingly, the maturation program induced by CT is unique since CT does not induce but rather inhibits cytokine (IL-12p70 and TNF-al pha) and chemokine (RANTES, MIP-1 alpha and MIP-1 beta) secretion by lipopo lysaccharide- or CD40 ligand-activated DC. Our results help to elucidate th e mechanism of action of CT as an adjuvant and highlight a new stimulus of bacterial origin that promotes maturation of DC.