UCD line 200 chickens develop an inherited autoimmune fibrotic disease, several features of which are similar to human progressive systemic sclerosis (SSc). The most striking features of this disease are mononuclear cell infiltrate in skin as well as hyperplasia of the media and intimal destruction of the arterial vessels, and fibrosis. These findings are found in skin, esophagus, heart, lung, testes, synovia, and other organs. Line 200 birds also develop antinuclear antibodies and antibodies to type II collagen. Using a detailed panel of monoclonal antibodies to avian mononuclear cell populations, we have demonstrated that early lesions show a significant CT4 cell infiltration followed by CT8 cells and an increase in B cell clusters. We have also developed an extensive panel of monoclonal antibodies to thymic stroma. These antibodies demonstrate that line 200 chickens have striking deficiencies in the normal thymic subcapsular architecture coupled with an excessive expression of MHC class II antigens, particularly in the cortex. In addition, line 200 chickens have a significant elevation of IL-2 receptor thymic density. These thymic lesions can be found as early as 18 days in ovo, long before any disease is manifest. We will build on the strengths of this model and attempt to study in detail select aspects of T cell differentiation and the role of soluble factors and accessory molecules in inducing fibroblast and endothelial cell destruction. In addition, we will use newly developed reagents to determine why line 200 thymocytes have increased IL-2R levels and whether monoclonal antibodies to CT4, CT8, B-L or B cells significantly alter disease expression. Further, because of the significant degree of dermal pathology, we will study in parallel the immunobiology of lesions by determining whether there are functional differences in dermal fibroblasts of line 200 chickens compared to controls. Similarly, we will determine whether mononuclear cells and/or mononuclear cell derived cytokines from line 200 or control birds influence the growth and biosynthetic function of line 200 and control derived fibroblasts. Finally, we will take advantage of the unique embryogenesis of the chicken and study factors produced by line 200 chickens which promote angiogenesis as well as to determine the basis of vascular occlusion in affected animals.

National Institute of Health (NIH)
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
Research Project (R01)
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General Medicine A Subcommittee 2 (GMA)
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University of California Davis
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United States
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