Induction of a type 1 regulatory CD4 T cell response following V(beta)8.2 DNA vaccination results in immune deviation and protection from experimental autoimmune encephalomyelitis

DNA vaccination has been used to generate effective cellular as well as hum oral immunity against target antigens, Here we have investigated the induct ion and involvement of regulatory T cell (T-reg) responses in mediating pre vention of experimental autoimmune encephalomyelitis (EAE), following vacci nation with plasmid DNA encoding the TCR V(beta)8.2 chain predominantly dis played on disease-causing lymphocytes, Vaccination with DNA encoding the wi ld-type TCR results in priming of type 1 CD4 T-reg and skewing of the globa l response to myelin basic protein in a T(h)2 direction, leading to signifi cant protection from disease. In contrast, vaccination with mutant DNA enco ding altered residues critically involved in recognition by the T-reg resul ts in priming of a type 2 regulatory response which fails to mediate immune deviation or protection from EAE, Control mice immunized with DNA, encodin g TCR with changes at an irrelevant site, were protected from antigen-induc ed disease. Furthermore, protection can be transferred into naive recipient s with CD4 T-reg from wildtype DNA-immunized mice but not from animals vacc inated with the mutant DNA. These data suggest that vaccination with plasmi d DNA encoding one or multiple V-beta genes can be exploited to enhance nat ural regulatory responses for intervention in autoimmune conditions.