CORRECTION OF ACCELERATED AUTOIMMUNE-DISEASE BY EARLY REPLACEMENT OF THE MUTATED LPR GENE WITH THE NORMAL FAS APOPTOSIS GENE IN THE T-CELLSOF TRANSGENIC MRL-LPR LPR MICE/

MRL-lpr/lpr mice develop a generalized autoimmune disease which includ es increased autoantibody production, glomerulonephritis, and developm ent of lymphadenopathy. The lpr genetic defect has been identified as a mutation in the Fas apoptosis gene that results in low expression of Fas mRNA. To determine the significance of the lpr mutation and T cel ls in the development of the autoimmune disease, we constructed transg enic MRL-lpr/lpr mice using a full-length murine Fas cDNA under the re gulation of the T-cell-specific CD2 promoter and enhancer. Here we sho w that the early correction of the lpr gene defect in T cells eliminat es glomerulonephritis and development of lymphadenopathy and decreases the levels of autoantibodies. In this model, early correction of the lpr defect in T cells is sufficient to eliminate the acceleration of a utoimmune disease even in the presence of B cells and other cells that express the mutant lpr gene.