Kochetkova I et al. (2008) Vaccination without autoantigen protects against collagen II-induced arthritis via immune deviation and regulatory T cells. J Immunol 181: 2741–2752

A Salmonella vector expressing colonization factor Ag I (CFA/I), which was developed as a diarrhea vaccine, has previously been shown to have anti-inflammatory properties. A study by Kochetkova et al. has now demonstrated that the vaccine provides protection from collagen-induced arthritis (CIA), a mouse model of rheumatoid arthritis (RA), by altering the function of type-II-collagen-specific CD4+ T cells.

The development of CIA was suppressed in DBA/1 mice that were orally immunized with Salmonella–CFA/I, compared with those that received vector-only or phosphate-buffered saline (control groups), as demonstrated by marked reductions in cartilage degeneration and proinflammatory cytokine production following challenge with type II collagen. Analysis of T cells purified from the lymph nodes of protected mice showed reduced proliferation of type-II-collagen-specific CD4+ T cells and increased production of regulatory cytokines, including interleukin (IL)-4 and TGF-β. Notably, neutralization of IL-10, TGF-β or IL-4 by monoclonal antibodies compromised the protective effect of Salmonella–CFA/I administration, highlighting the important role of these cytokines in the suppression of CIA. Adoptive transfer experiments after CIA induction showed that both CD4+CD25− and CD4+CD25+ T-cell subsets confer protection and suppress production of IL-17, IL-27 and tumor necrosis factor, but the effect is optimal with total CD4+ T cells.

The results of this study show that Salmonella–CFA/I vaccine has the therapeutic potential to suppress the development of CIA in susceptible mice.