Suppressive vaccination with DNA encoding a variable region gene of the T-cell receptor prevents autoimmune encephalomyelitis and activates Th2 immunity

A variable region gene of the T-cell receptor, Vβ8.2, is rearranged, and its product is expressed on pathogenic T cells that induce experimental autoimmune encephalomyelitis (EAE) in H-2(u) mice after immunization with myelin basic protein (MBP). Vaccination of these mice with naked DNA encoding Vβ8.2 protected mice from EAE. Analysis of T cells reacting to the pathogenic portion of the MBP molecule indicated that in the vaccinated mice there was a reduction in the Th1 cytokines interleukin-2 (IL-2) and interferon-γ. 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 autoimmune disease, reversal of the autoimmune response from Th1 to Th2, may make this approach attractive for treatment of Th1- mediated diseases like multiple sclerosis, juvenile diabetes and rheumatoid arthritis.