International Immunology, Vol. 13, No. 6, 835-841,
June 2001
© 2001 Japanese Society for Immunology
Induction of a type 1 regulatory CD4 T cell response following Vß8.2 DNA vaccination results in immune deviation and protection from experimental autoimmune encephalomyelitis
Department of Microbiology and Molecular Genetics, University of California, Los Angeles, CA 90095, USA
1 Division of Immune Regulation, La Jolla Institute for Allergy and Immunology, 10355 Science Center Drive, San Diego, CA 92121, USA
2 Center for Immunology and Cancer Immunobiology Center, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA
Correspondence to: V. Kumar
DNA vaccination has been used to generate effective cellular as well as humoral immunity against target antigens. Here we have investigated the induction and involvement of regulatory T cell (Treg) responses in mediating prevention of experimental autoimmune encephalomyelitis (EAE), following vaccination with plasmid DNA encoding the TCR Vß8.2 chain predominantly displayed on disease-causing lymphocytes. Vaccination with DNA encoding the wild-type TCR results in priming of type 1 CD4 Treg and skewing of the global response to myelin basic protein in a Th2 direction, leading to significant protection from disease. In contrast, vaccination with mutant DNA encoding altered residues critically involved in recognition by the Treg results in priming of a type 2 regulatory response which fails to mediate immune deviation or protection from EAE. Control mice immunized with DNA, encoding TCR with changes at an irrelevant site, were protected from antigen-induced disease. Furthermore, protection can be transferred into naive recipients with CD4 Treg from wild-type DNA-immunized mice but not from animals vaccinated with the mutant DNA. These data suggest that vaccination with plasmid DNA encoding one or multiple Vß genes can be exploited to enhance natural regulatory responses for intervention in autoimmune conditions.
Keywords: DNA vaccine, experimental autoimmune encephalomyelitis, regulatory T cells, TCR, Th1/Th2
Transmitting editor: L. Steinman
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