Vaccination with TNF-α modulated DCs protects against CIA in an antigen-specific manner

Background and Objective

Dendritic Cells (DCs) play an important role in initiation and regulation of immune responses in arthritis, because these cells are crucial for the initiation of T cell immunity. Full mobilization of effector T cells depends on proper maturation of DCs. Current evidence indicates that the type of T cell response indeed crucially depends on the activation status of DC. For example, antigen recognition on resting DCs can result in immuneregulation. In this study we explored the immunological effects of differentially matured DCs on the development of collagen-induced arthritis (CIA).

Methods

Bone marrow derived DCs were cultured in the presence of GM-CSF with or without IL-4. Immature, TNF-α or LPS activated, antigen-pulsed DCs were used. At several time points before immunization with bovine CII protein, mice were injected with DCs exposed to these different maturation stimuli. Mice were boosted on day 21 post-CII-immunization and disease course was monitored.

Results

Although vaccination with immature or LPS activated DCs had no significant influence on disease course, administration of antigen-loaded, TNF-α modulated DCs resulted in a delayed onset of arthritis and a decreased clinical score. The effect was antigen-specific, as also evidenced when antibody titres were measured. A specific increment in the collagen-specific 'Th1-associated' IgG_2a response was observed. Remarkably, IgG₁ was unaffected by this vaccination.

Conclusions

CIA can be prevented through vaccination with TNF-α matured DCs in an antigen-specific manner. These findings provide a rational to employ DCs in treatment or prevention of arthritis.