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Regulatory T Cell Vaccination without Autoantigen Protects against Experimental Autoimmune Encephalomyelitis¹

Veterinary Molecular Biology, Montana State University, Bozeman, MT 59717

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_reg 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-, 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.

The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

¹ This work was supported by Public Health Service Grant AI-41123 and in part by Montana Agricultural Station and U.S. Department of Agriculture Formula Funds. The Veterinary Molecular Biology flow cytometry facility was in part supported by National Institutes of Health/National Center for Research Resources Centers of Biomedical Research Excellence P20 RR-020185.

² Address correspondence and reprint requests to Dr. David W. Pascual, Veterinary Molecular Biology, P.O. Box 173610, Montana State University, Bozeman, MT 59717-3610. E-mail address: dpascual{at}montana.edu

³ Abbreviations used in this paper: MS, multiple sclerosis; CFA/I, colonization factor Ag I; CLN, cervical lymph node; CM, complete medium; EAE, experimental autoimmune encephalomyelitis; HNLN, head and neck lymph node; LFB, luxol fast blue; MLN, mesenteric lymph node; PLP, protein proteolipid; PP, Peyer patches; PT, Bordetella pertussis toxin; SMLN, submaxillary gland lymph node; T_eff, effector T; T_reg, regulatory T.

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