Oral Salmonella vaccine expressing enterotoxigenic E. coli colonization factor antigen 1 (CFA/I) fimbriae induced production of Treg cells. Adoptive transfer of CD25+ Treg cells obtained from oral Salmonella-CFA/I-vaccinated mice conferred superior protection to proteolipid protein (PLP)139-151-dependent EAE to those from Salmonella vector-immunized mice; this was attributed to their differential cytokine profiles. Salmonella-CFA/I-vaccinated mice produced more TGF-β than Salmonella vector-immunized mice. To test the hypothesis Salmonella-CFA/I-induced Treg cells, independent of PLP-specificity, confers protection via TGF-β, SJL/J mice were immunized with either Salmonella-CFA/I or Salmonella vector. Two wks later, CD25+ and CD25- CD4+ T cells were sorted, adoptively transferred to naïve SJL/J mice, concomitantly treated with anti-TGF-β mAb or isotype IgG, and then induced with EAE. Mice adoptively transferred with Treg cells neutralized of their TGF-β showed earlier disease onset and greater disease severity than mice adoptively transferred with Treg cells treated with IgG control. Moreover, greater proinflammatory cytokine production was observed. This work shows Treg cells can be induced to high potency by simply vaccinating against irrelevant Ags using a live, bacterial vaccine, thus, offering a novel approach to treat autoimmune diseases independent of the auto-Ag. Supported by NIH AI-41123.
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