Induction of protective therapy for autoimmune diseases by targeted DNA vaccines encoding pro-inflammatory cytokines and chemokines.
T-cell-mediated autoimmune diseases such as multiple sclerosis, rheumatoid arthritis or type 1 diabetes result from an aggressive attack of self-components by autoimmune T-cells. Pro-inflammatory mediators, particularly cytokines and chemokines, direct the homing and effectorfunction of these cells. It has recently been demonstrated that the immune system, which can attack self-components, also generates 'beneficial' autoimmunity against pro-inflammatory mediators. During the course of an autoimmune condition, and to a much lesser extent in response to microbial inflammation, the immune system produces auto-antibodies to pro-inflammatory mediators. This reduces the harm from these diseases. We also discovered that targeted DNA vaccines could effectively amplify these responses to provide protective immunity. The underlying mechanism is partially understood. At the site of immunization, the relevant gene product is produced and then presented by dendritic cells/macrophages, which undergo activation due to an interaction of plasmid CpG with toll-like receptor 9 on the dendritic cell. This then activates CD4+ T-cells, which help the production of T-cell-dependent antibodies against the gene product of the vaccines. These antibodies neutralize their target product and suppress inflammation. This review explores this interesting concept and its therapeutic implications.
Karin
Nathan
N
Technion-Israel Institute of Technology, Department of Immunology, Haifa 31096, Israel. nkarin@techunix.technion.ac.il
D000818:Animals; D000906:Antibodies / Q000276:immunology; D001169:Arthritis, Experimental / Q000628:therapy; D001172:Arthritis, Rheumatoid / Q000628:therapy; D001327:Autoimmune Diseases / Q000276:immunology / Q000628:therapy*; D018925:Chemokines / Q000276:immunology*; D016207:Cytokines / Q000276:immunology*; D003713:Dendritic Cells / Q000276:immunology; D006801:Humans; D007249:Inflammation / Q000276:immunology*; D008213:Lymphocyte Activation; D008264:Macrophages / Q000276:immunology; D008954:Models, Biological; D009103:Multiple Sclerosis / Q000628:therapy; D013601:T-Lymphocytes / Q000276:immunology; D019444:Vaccines, DNA / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology / Q000627:therapeutic use*
D000906:Antibodies; D018925:Chemokines; D016207:Cytokines; D019444:Vaccines, DNA