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Protection Against Experimental Autoimmune Encephalomyelitis Generated by a Recombinant Adenovirus Vector Expressing the V8.2 TCR Is Disrupted by Coadministration with Vectors Expressing Either IL-4 or -10¹

Todd A. Braciak^2,*, Brian Pedersen^*, Judy Chin, Clay Hsiao, E. Sally Ward, Igor Maricic^*, Alex Jahng^*, Frank L. Graham, Jack Gauldie, Eli E. Sercarz^* and Vipin Kumar^*

^* Division of Immune Regulation, La Jolla Institute for Allergy and Immunology, San Diego, CA 92121; Department of Microbiology and Cancer Immunobiology Center, University of Texas Southwestern Medical Center, Dallas, TX 75235; Department of Microbiology and Molecular Genetics, University of California, Los Angeles, CA 90024; and Department of Pathology, McMaster University, Hamilton, Ontario, Canada

Adenovirus vectors are increasingly being used for genetic vaccination and may prove highly suitable for intervention in different pathological conditions due to their capacity to generate high level, transient gene expression. In this study, we report the use of a recombinant adenovirus vector to induce regulatory responses for the prevention of autoimmune diseases through transient expression of a TCR -chain. Immunization of B10.PL mice with a recombinant adenovirus expressing the TCR V8.2 chain (Ad5E1 mV8.2), resulted in induction of regulatory type 1 CD4 T cells, directed against the framework region 3 determinant within the B5 peptide (aa 76–101) of the V8.2 chain. This determinant is readily processed and displayed in an I-A^u context, on ambient APC. Transient genetic delivery of the TCR V8.2 chain protected mice from Ag-induced experimental autoimmune encephalomyelitis. However, when the Ad5E1 mV8.2 vector was coadministered with either an IL-4- or IL-10-expressing vector, regulation was disrupted and disease was exacerbated. These results highlight the importance of the Th1-like cytokine requirement necessary for the generation and activity of effective regulatory T cells in this model of experimental autoimmune encephalomyelitis.

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