Immunotherapy through injection of immature dendritic cells prevents collagen-induced arthritis

Background

Dendritic cells (DCa) play an important role for initiation and regulation of immune response in arthritis. Immature DCs with a low expression of MHC class II and of coactivation molecules CD86 have a tolerigenic potential in vivo. Previous studies have shown that genetically modified DCs and TNF-α-matured DCs may prevent autoimmune diseases or allograft rejection.

Objective

Therefore, we explored the immunological effects of differentially matured DCs on the development of collagen-induced arthritis in mice.

Methods

Murine bone-marrow-derived DCs where cultured in the presence of granulocyte/macrophage-colony-stimulating factor and IL-4 and incubated with collagen type II (CII). Maturation of the DCs was blocked with IL-10, or induced with TNF-α or lipopolysaccharide (LPS). The DC differentiation and maturation steps were controlled by CD11c and CD86 expression, which was assessed by flow cytometry. Seven days before immunisation with bovine CII, mice were injected intraperitoneally with 500,000 DCs obtained at different stages of maturation. Mice were boosted on day 21 after arthritis induction and the disease course was monitored until day 43. DC function was assessed through mlR assays.

Results

While injection with IL-10-blocked or LPS-matured DCs had no significant influence on the onset and development of arthritis, administration of TNF-matured DCs resulted in a reduction of arthritis severity in comparison with the control group. In contrast, mice treated with immature DCs showed a delayed arthritis onset and a decrease in the arthritis clinical score.

Conclusions

Collagen-induced arthritis may be prevented by pretreatment with antigen-specific immature DCs or TNF-matured DCs. Furthermore, the principle of DC-mediated tolerance may have promising immunotherapeutic potential in arthritis.