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.

Agency
National Institute of Health (NIH)
Institute
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
Type
Research Project (R01)
Project #
2R01AR036867-04
Application #
3157788
Study Section
General Medicine A Subcommittee 2 (GMA)
Project Start
1987-07-01
Project End
1993-06-30
Budget Start
1990-07-15
Budget End
1991-06-30
Support Year
4
Fiscal Year
1990
Total Cost
Indirect Cost
Name
University of California Davis
Department
Type
Schools of Medicine
DUNS #
094878337
City
Davis
State
CA
Country
United States
Zip Code
95618
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Van de Water, J; Boyd, R; Wick, G et al. (1994) The immunologic and genetic basis of avian scleroderma, an inherited fibrotic disease of line 200 chickens. Int Rev Immunol 11:273-82
Chang, C C; Greenspan, A; Gershwin, M E (1993) Osteonecrosis: current perspectives on pathogenesis and treatment. Semin Arthritis Rheum 23:47-69
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Duncan, M R; Wilson, T J; Van De Water, J et al. (1992) Cultured fibroblasts in avian scleroderma, an autoimmune fibrotic disease, display an activated phenotype. J Autoimmun 5:603-15
Wilson, T J; Van de Water, J; Mohr, F C et al. (1992) Avian scleroderma: evidence for qualitative and quantitative T cell defects. J Autoimmun 5:261-76
Gruschwitz, M S; Moormann, S; Kromer, G et al. (1991) Phenotypic analysis of skin infiltrates in comparison with peripheral blood lymphocytes, spleen cells and thymocytes in early avian scleroderma. J Autoimmun 4:577-93
Boyd, R L; Wilson, T J; Van De Water, J et al. (1991) Selective abnormalities in the thymic microenvironment associated with avian scleroderma, an inherited fibrotic disease of L200 chickens. J Autoimmun 4:369-80
Wilson, T J; Van de Water, J; Boyd, R L et al. (1991) Abnormalities associated with the bursal microenvironment in spontaneous dysgammaglobulinemia of UCD line 140 chickens. Clin Immunol Immunopathol 59:208-21

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