MODULATION OF EXPERIMENTAL ARTHRITIS IN MICE BY GPI-ANCHORED PROTEIN TRANSFER

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Collagen-induced arthritis (CIA) in mice is an experimental model of rheumatoid arthritis (RA) that closely mimics the human disorder both clinically and immunopathologically. As in human RA, susceptibility to the disease maps to a subregion (the I-A) of class II MHC and injury to cartilage type II collagen results from both T cell-mediated and humoral immune mechanisms. A recently emerging body of evidence has indicated that one class of cell surface proteins has the unusual property, both in vitro and in vivo, of being able to transfer from one cell type to another. The proteins that possess this capability are proteins that are membrane- anchored by glycoinositolphospholipid (GPI) units. Importantly, it additionally has been demonstrated that these proteins, when purified and added directly to cells, insert themselves into the target cells, and once incorporated, are fully functional. Among the proteins in this class are two critical inhibitors of humoral immune attack [the decay accelerating factor (DAF) or CD55 and the membrane inhibitor of reactive lysis (MIRL) or CD59]. By recombinant DNA technology, it has been shown that it is possible to re-engineer other key regulators of humoral and cellular immune attack so as to possess GPI anchors. This feasibility study is directed at examining new experimental methods for delivery of these GPI- containing regulators to inflamed joints using both transgenic animals expressing the proteins and the purified proteins themselves. The data obtained could have relevance to new treatment modalities for RA and other rheumatic diseases.