Regulatory T-cell vaccination independent of auto-antigen

To date, efforts to treat autoimmune diseases have primarily focused on the disease symptoms rather than on the cause of the disease. In large part, this is attributed to not knowing the responsible auto-antigens (auto-Ags) for driving the self-reactivity coupled with the poor success of treating autoimmune diseases using oral tolerance methods. Nonetheless, if tolerogenic approaches or methods that stimulate regulatory T (T(reg)) cells can be devised, these could subdue autoimmune diseases. To forward such efforts, our approach with colonization factor antigen I (CFA/I) fimbriae is to establish bystander immunity to ultimately drive the development of auto-Ag-specific T(reg) cells. Using an attenuated Salmonella vaccine expressing CFA/I fimbriae, fimbriae-specific T(reg) cells were induced without compromising the vaccine's capacity to protect against travelers' diarrhea or salmonellosis. By adapting the vaccine's anti-inflammatory properties, it was found that it could also dampen experimental inflammatory diseases resembling multiple sclerosis (MS) and rheumatoid arthritis. Because of this bystander effect, disease-specific T(reg) cells are eventually induced to resolve disease. Interestingly, this same vaccine could elicit the required T(reg) cell subset for each disease. For MS-like disease, conventional CD25(+) T(reg) cells are stimulated, but for arthritis CD39(+) T(reg) cells are induced instead. This review article will examine the potential of treating autoimmune diseases without having previous knowledge of the auto-Ag using an innocuous antigen to stimulate T(reg) cells via the production of transforming growth factor-β and interleukin-10.