Role of autoreactive CD8(+) T cells in organ-specific autoimmune diseases:insight from transgenic mouse models

There is now convincing evidence that autoreactive CD8(+) T cells can contr ibute to the pathogenesis of organ-specific autoimmune diseases. In the non -obese diabetic mouse, there is direct evidence that beta-islet cell-specif ic CD8(+) cytotoxic T cells have a pathogenic effect. In human diseases suc h as autoimmune diabetes and multiple sclerosis, indirect evidence also sug gests a role for CD8(+) T cells in tissue damage, although their antigen sp ecificity is unknown. Transgenic mouse models as well as the use of knockou t mice have been instrumental in the identification of the role of autoreac tive CD8(+) T cells. Spontaneous models of CD8(+) T-cell-mediated autoimmun ity generated through transgenesis should help delineate the effector mecha nisms leading to tissue destruction. The study of autoreactive CD8(+) T cel ls and the characterization of their antigenic specificity should help unra vel the pathophysiology of organ-specific autoimmune diseases, help identif y exacerbating foreign antigens, and allow the design of antigen-specific i mmunotherapy targeting the pathogenic autoreactive T cells.