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.
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