This project will explore an experimental model of scleroderma in the mouse. The model is based on (a) the probable involvement of autoimmune immunopathologic processes in idiopathic scleroderma, and (b) the production of a scleroderma-like illness in human graft-versus-host disease (GVHD), as well as in chronic GVHD in rodents. We plan to define the requirements for establishing and boosting a chronic GVHD in mice across various histocompatibility barriers. We will follow skin histopathology and autoimmune antibodies, and will study the role of the thymus and of cyclophosphamide on GVHD. The modulation of skin changes, including fibronectin deposition, and the effects of bleomycin will be measured. These studies should provide insight into the nature of the changes found in idiopathic scleroderma (progressive systemic sclerosis) and on the tissue injury seen in chronic GVHD.
