CD4+CD25+Foxp3+ regulatory T cells induced by the immunization with tolerogenic dendritic cells atenuate collagen-induced arthritis symptoms in DBA/1j mice.

CARRANZA F; FALCON C; CERVI L

Congreso; First French-Argentine Immunology Congress LVIII Reunión científica de la Sociedad Argentina de Inmunología.; 2010

SAI

Dendritic cells (DC) are professional antigen-presenting cells that maintain immune tolerance to self-antigens by controlling the pathogenicity of auto-reactive T-cells. DC cell-based immunotherapies are a great promise for the restoration of tolerance in autoimmune disease. Besides, these cells can be modified ex vivo to induce tolerogenic function and in this way they are able to inhibit inflammatory responses in autoimmune diseases. Previous results showed that the treatment of DBA/1J mice bone marrow derived DC with a total extract of the helminth parasite Fasciola hepatica (TE) plus CpG (TE/CpG), induce tolerogeneic properties in these cells such as a decrease in pro-inflammatory cytokine production, an increase in anti-inflammatory cytokine production and a high expression of indoleamine 2,3-dioxigenasa (IDO). Furthermore, the immunization of DBA/1J mice with TE/CpG-treated DC was able to ameloriate the symptoms of collagen-induced arthritis (CIA). The aim of this work was to evaluate the involvement of CD4+Foxp3+ regulatory T cells in the mechanism by which the immunization of mice with TE/CpG-treated DC diminishes the symptoms of CIA. The treatment of mice with TE/CpG-treated DC induced an increase in the percentage of CD4+Foxp3+ CD25+, determined by flow citometry in draining lymph nodes (DLN), compare to the positive controls of CIA (PBS injected mice). Besides, the recipient mice of TE/CpG-treated DC showed a significant increase in IL-10 production as well as a decrease in INF-g production detected by ELISA in the supernatants of DLN after 48 hs of culture compared to PBS injected mice (positive control) (Student T test p < 0.05). Additionally, the levels of IL-17 and TGF-b were not modified in the supernatants of DLN from recipient mice of TE/CpG-treated DC. The IL-17/IL-10, IFN-g/IL-10, IFN-g/TGF-b ratios of cytokines detected in DLN of  mice injected with TE/CpG-treated DC were significantly lower than those obtained with other treatments (Student T test p < 0.05). Finally, an attenuation of the CIA symptoms (score, incidence and severity) was observed in the recipient mice of  CD4+ CD25+ T cells sorted from DLN of mice that had been injected with TE/CpG-treated DC, compared with control (mice injected with PBS). Our data show that TE/CpG-treated DC are able to induce in vivo a CD4+Foxp3+ CD25+ T regulatory cells population, which are functionally effective to prevent the symptoms of CIA through a mechanism where IL-10 is probably involved.