Abstract
Transgenic mice overexpressing IFN-gamma in the epidermis develop an inflammatory skin disease resembling cutaneous lupus erythematosus shortly after birth. By 3 months of age, most female transgenics develop a lupus-like syndrome characterised by production of IgG anti-dsDNA, antihistone and antinucleosome autoantibodies. The autoantibodies are nephritogenic, with one-third of females developing a severe immune complex mediated glomerulonephritis. Analysis of these transgenics suggests that pathogenic autoantibodies arise via an antigen-driven T-cell-dependent mechanism with apoptotic keratinocytes acting as a potential source of autoantigen. The mechanism of autoantibody production in IFN-gamma transgenics may be relevant to human lupus and is consistent with a central role for cutaneous T cells in the pathogenesis of systemic lupus erythematosus in man.