T cell activation after priming by immune complex matured porcine monocytic-derived dendritic cells

F4+ enterotoxigenic E. coli (ETEC) adhere with their F4 fimbriae to an F4-specific receptor, colonise the small intestine and cause diarrhoea in recently weaned piglets. Our group has demonstrated that oral immunisation of piglets with purified F4 fimbriae induces a robust F4-specific immune response, protecting these piglets against a subsequent F4+ ETEC infection. However, to protect against postweaning diarrhoea, immunisation should already occur during the suckling period. At this age, oral immunisation could be complicated due to the immature status of the immune system. Furthermore, F4 fimbriae only partially mature intestinal dendritic cells. A possible solution could be antigen targeting to Fc receptors (FcR) present on antigen presenting cells, as this can enhance both the cellular and humoral immune response. Therefore we determined the effects of F4-IgG immune complexes (IC) on maturation of porcine monocytic-derived dendritic cells (MoDC). IC treatment resulted in an increased expression of MHCII and of the costimulatory molecules CD80/86 and CD40 as compared to F4 and IgG treated cells. Moreover, IC stimulation downregulated both the phagocytic (OVA-dQ) and endocytic capacity (FITC-dextran), whereas F4 and IgG stimulation only resulted in a moderate reduction. These data suggest that IC stimulation enhances the maturation of porcine MoDC. Mature MoDC secrete a wide range of cytokines, which influence the differentiation and polarization of T cells, thereby determining the outcome of adaptive immune responses. IC matured MoDC secreted higher levels of IL-1β, IL-6, IL-8, IL-12p40 and TNFα cytokines as compared to F4 and IgG treated MoDC. To further investigate whether the observed mature phenotype of IC treated MoDC correlate with their capacity to stimulate T cells, MoDC were cocultured with allogeneic T lymphocytes. Thus, IC matured MoDC were more effective at activating allogeneic T cells in comparison to F4 and IgG treated cells. These findings clearly indicate that antigen targeting to FcR enhances the maturation of porcine MoDC and that this maturation involves a heightened secretion of several inflammatory cytokines, which enables IC treated DC to activate T cells in a more profound manner