No abstract

Dendritic cells (DC) have the potential to control the outcome of autoimmunity by modulating the immune response. In this study, we tested the ability of Fasciola hepatica total extract (TE) to induce tolerogenic properties in CpG-ODN (CpG) maturated DC, to then evaluate the therapeutic potential of these cells to diminish the inflammatory response in collagen induced arthritis (CIA). DBA/1J mice were injected with TE plus CpG treated DC (T/C-DC) pulsed with bovine collagen II (CII) between two immunizations with CII and clinical scores CIA were determined. The levels of CII-specific IgG2 and IgG1 in sera, the histological analyses in the joints, the cytokine profile in the draining lymph node (DLN) cells and in the joints, and the number, and functionality of CD4+CD25+Foxp3+ T cells (Treg) were evaluated. Vaccination of mice with CII pulsed T/C-DC diminished the severity and incidence of CIA symptoms and the production of the inflammatory cytokine, while induced the production of anti-inflammatory cytokines. The therapeutic effect was mediated by Treg cells, since the adoptive transfer of CD4+CD25+ T cells, inhibited the inflammatory symptoms in CIA. The in vitro blockage of TGF-β in cultures of DLN cells plus CII pulsed T/C-DC inhibited the expansion of Treg cells. Vaccination with CII pulsed T/C-DC seems to be a very efficient approach to diminish exacerbated immune response in CIA, by inducing the development of Treg cells, and it is therefore an interesting candidate for a cell-based therapy for rheumatoid arthritis (RA).

Dendritic cells (DCs) can function as adjuvants able to mediate protection against different pathogens. Given that successful vaccination against Fasciola hepatica is mostly related to the induction of Th1 responses, we studied the potential of DCs loaded with F. hepatica antigens and lipopolysaccharide (LPS) (which promote DCs maturation) as a vaccine against fasciolosis in BALB/c mice. However, only a semimature phenotype was achieved when DCs were simultaneously cultured with an F. hepatica total extract (TE) and LPS. The activation status of TE-loaded DCs was enhanced when these cells were treated with TE 90 minutes before being stimulated with LPS (TE90 DCs). More importantly, a single vaccination of mice with TE90 DCs stimulated a systemic Th1 response and conferred protection against hepatic damage induced by F. hepatica infection. Thus, TE90 DCs may prove to be a useful new tool for vaccination against F. hepatica.