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

CARRANZA FRANCO; FALCÓN CRISTIAN; CERVI LAURA

Capital federal

Congreso; First French - Argentine Immunology Congress; 2010

Sociedad Argentina de Inmunología

Dendritic cells (DC) are professional antigen-presenting cells that maintain immune tolerance to self-antigens by controlling the pathogenicity of auto-reactive T-cells. These cells can be modified ex vivo to induce tolerogenic function and inhibit inflammatory responses in autoimmune diseases. Previous results show that the treatment of DBA/1J mice bone marrow derived DC with a total extract of the parasite Fasciola hepatica (TE) plus CpG (T/C) induces tolerogeneic properties such as a decrease in pro-inflammatory cytokine production, an increases in anti-inflammatory cytokine production and a high expression of indoleamine 2,3-dioxigenasa (IDO). Furthermore, the immunization of DBA/1J mice with T/C-treated DC was able to ameliorate 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 T/C-treated DC diminishes the symptoms of CIA. The immunization of mice with T/C-treated DC induced an increase in the percentage of CD4+CD25+Foxp3+ T cells, determined by flow citometry in draining lymph nodes (DLN), compare to the control (PBS injected mice). Besides, the recipient mice of T/C-treated DC showed a significant increase in IL-10 production as well as a decrease in INF-g production detected in the supernatants of DLN of culture compared to the control (p<0.05). Additionally, the levels of IL-17 and TGF-b were not modified. In this cultures the IL-17/IL-10, IFN-g/IL-10, IFN-g/TGF-b ratios were significantly lower than those obtained with other treatments (p<0.05). Finally, an attenuation of the CIA symptoms was observed in the recipient mice of  CD4+ CD25+ T cells sorted from DLN of mice that had been injected with T/C-treated DC, compared with control. Our data show that T/C-treated DC are able to induce in vivo a CD4+CD25+Foxp3+ T regulatory cells population, which are functionally effective to prevent the symptoms of CIA.