Regulatory T cell vaccination without autoantigen protects against experimental autoimmune encephalomyelitis

Regulatory T (T-reg) cells show promise for treating autoimmune diseases, but their induction to elevated potency has been problematic when the most optimally derived cells are from diseased animals. To circumvent reliance on autoantigen-reactive T-reg cells, stimulation to myelin-independent Ags may offer a viable alternative while maintaining potency to treat experimental autoimmune encephalomyelitis (EAE). The experimental Salmonella vaccine expressing colonization factor Ag I possesses anti-inflammatory properties and, when applied therapeutically, reduces further development of EAE in SJL mice. To ascertain T-g cell dependency, a kinetic analysis was performed showing increased levels of FoxP3(+)CD25(+)CD4(+) T cells. Inactivation of these T-reg cells resulted in loss of protection. Adoptive transfer of the vaccine-induced T-reg cells protected mice against EAE with greater potency than naive or Salmonella vector-induced T-reg cells, and cytokine analysis revealed enhanced production of TGF-beta, not IL-10. The development of these T-reg cells in conjunction with immune deviation by Th2 cells optimally induced protective T-reg cells when compared those induced in the absence of Th2 cells. These data show that T-reg cells can be induced to high potency to non-disease-inducing Ags using a bacterial vaccine.