Molecular and cellular basis for designing gene vaccines against inflammatory autoimmune disease

Organ-specific autoimmune diseases, such as psoriasis, rheumatoid arthritis, multiple sclerosis and autoimmune diabetes, are initiated by aberrant activation of interferon-γ (IFN-γ)-producing T helper 1 (Th1) cells that recognize self-peptides expressed inside these organs. Together, these diseases affect 3–5% of the population. Predisposing factors, such as susceptibility genes and environmental factors, are difficult to influence, and hence research has focused on the deviation of disease-inducing IFN-γ-producing Th1 cells into an interleukin-4-producing T helper 2 (Th2) cell phenotype with anti-inflammatory properties. Such immune deviation was first established as a therapy in mice and recently as therapy for humans suffering from inflammatory autoimmune disease. In the future, DNA-based vaccines might allow the induction of Th2 cells that protect against inflammatory autoimmune disease, thereby establishing safe and specific immune therapies.