SUPPRESSIVE VACCINATION WITH DNA ENCODING A VARIABLE REGION GENE OF THE T-CELL RECEPTOR PREVENTS AUTOIMMUNE ENCEPHALOMYELITIS AND ACTIVATESTH2 IMMUNITY

A variable region gene of the T-cell receptor, V beta 8.2, is rearrang ed, and its product is expressed on pathogenic T cells that induce exp erimental autoimmune encephalomyelitis (EAE) in H-2(u) mice after immu nization with myelin basic protein (MBP). Vaccination of these mice wi th naked DNA encoding V beta 8.2 protected mice from EAE. Analysis of T cells reacting to the pathogenic portion of the MBP molecule indicat ed that in the vaccinated mice there was a reduction in the Th1 cytoki nes interleukin-2 (IL-2) and interferon-gamma. In parallel, there was an elevation in the production of IL-4, a Th2 cytokine associated with suppression of disease. A novel feature of DNA immunization for autoi mmune disease, reversal of the autoimmune response from Th1 to Th2, ma y make this approach attractive for treatment of Th1-mediated diseases like multiple sclerosis, juvenile diabetes and rheumatoid arthritis.