CD8alpha+ dendritic cells enhance the antigen-specific CD4+ T-cell response and accelerate development of collagen-induced arthritis

To investigate the role of CD8α+ DCs in the development of collagen-induced arthritis (CIA). The immunogenic properties of CD8α+ and CD8α− DC subsets were investigated by mixed-lymphocyte reaction and cytokine enzyme-linked immunoassay. CII-pulsed CD8α+ DCs or CD8α− DCs with CD4+ T cells from CIA mice were adoptively transferred onto the hind footpad of DBA mice. The onset of arthritis and the arthritis index were examined for 14 weeks after adoptive transfer. Expression of MHC-II and CD80 but not CD86 and CD40 was higher in CD8α+ DCs than in CD8α− DCs from the spleens of CIA mice. Culturing CD8α+ DCs with CD4+ T cells significantly increased the proliferative response of CD4+ T cells in the presence of CII. The production of interleukin (IL)-12p70, IL-17, interferon (IFN)-γ, and tumor necrosis factor (TNF)-α was slightly increased in CD8α+ DCs than in CD8α− DCs. DBA/1 mice that were adoptively transferred with CII-pulsed CD8α+ DCs and CD4+ T cells into the footpads showed accelerated onset of CIA compared to control group. By contrast, CD8α− DCs showed a partial inhibitory effect on CIA. These findings show that CD8α+ DCs accelerated the onset of CIA when aoptively transferred with CD4+ T cells and that CD8α+ DCs provoke the development of CIA probably by stimulating the immune responses of CII-reactive CD4+ T cells and by increasing the production of inflammatory cytokines.