Suppressive immunization with DNA encoding a self-peptide prevents autoimmune disease: Modulation of T cell costimulation

Usually we rely on vaccination to promote an immune response to a pathogeni c microbe. In this study, we demonstrate a suppressive form of vaccination, with DNA encoding a minigene for residues 139-151 of myelin proteolipid pr otein (PLP139-151), a pathogenic self-Ag. This suppressive vaccination atte nuates a prototypic autoimmune disease, experimental autoimmune encephalomy elitis, which presents clinically with paralysis. Proliferative responses a nd production of the Th1 cytokines, IL-2 and IFN-gamma, were reduced in T c ells responsive to PLP139-151. In the brains of mice that were successfully vaccinated, mRNA for IL-2, IL-15, and IFN-gamma were reduced. A mechanism underlying the reduction in severity and incidence of paralytic autoimmune disease and the reduction in Th1 cytokines involves altered costimulation o f T cells; loading of APCs with DNA encoding PLP139-151 reduced the capacit y of a T cell line reactive to PLP139-151 to proliferate even in the presen ce of exogenous CD28 costimulation. DNA immunization with the myelin minige ne for PLP-altered expression of B7.1 (CD80), and B7.2 (CD86) on APCs in th e spleen. suppressive immunization against self-Ags encoded by DNA may be e xploited to treat autoimmune diseases.