University of California line 200 chickens are an inbred colony that develop an inherited fibrotic disease which has many similarities to human progressive systemic sclerosis. These animals represent an excellent model for the study of the potential contribution of immunoregulatory defects and abnormal lymphocyte differentiation to the predisposition to autoimmune diseases and fibrosis. These chickens arose after nearly 40 years of inbreeding and selection of the most severely affected animals. The lesions of these birds form a syndrome characterized by small vessel narrowing, skin and progressive internal organ fibrosis, pericardial fusions, polyarthritis and the presence of antinuclear antibodies and antibodies to extractable nuclear antigens. The development of a wide variety of autoantibodies, the early appearance of Ia+ cells, and accelerated B cell maturation, suggests that the immune disorder may not be antigen specific and is more reflective of a major defect(s) in immunoregulation. We have now developed an MHC compatible line with a different Ig allotype, permitting careful and detailed cell transfer experiments. Further, we now have available an extensive and will studied library of monoclonal antibodies against chicken T cells, B cells, macrophages and stromal cells. This will allow us to focus our attention on the genetic basis of this disease as well as on immune regulation, with particular emphasis on ontogeny. Specifically, we will study and characterize the immune basis and the natural history of disease development by thymectomy and bursectomy. We will also characterize thymic and bursal ontogeny with our library of monoclonal reagents. Similarly, we will examine IL-2 production and utilization and the development of soluble suppressor factors during blast transformation. Finally, we will attempt to transfer disease with lymphoid cells to MHC compatible recipients. Our studies on genetics and on immune regulation should lead to a clearer understanding of the immunological abnormalities of these chickens and will allow us, in future studies, to define experiments required to understand the interaction of the immune system and the fibrosis.

National Institute of Health (NIH)
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
Research Project (R01)
Project #
Application #
Study Section
General Medicine A Subcommittee 2 (GMA)
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
University of California Davis
Schools of Medicine
United States
Zip Code
Duncan, M R; Berman, B; Van de Water, J et al. (1995) Mononuclear cells isolated from fibrotic skin lesions in avian scleroderma constitutively produce fibroblast-activating cytokines and immunoglobulin M. Int Arch Allergy Immunol 107:519-26
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
Brezinschek, H P; Gruschwitz, M; Sgonc, R et al. (1993) Effects of cytokine application on glucocorticoid secretion in an animal model for systemic scleroderma. J Autoimmun 6:719-33
Wilson, T J; Davidson, N J; Boyd, R L et al. (1992) Phenotypic analysis of the chicken thymic microenvironment during ontogenic development. Dev Immunol 2:19-27
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

Showing the most recent 10 out of 12 publications