IMMUNOREGULATION IN AVIAN SCLERODERMA

Project: Research project

Project Details

Description

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.
StatusFinished
Effective start/end date7/1/876/30/97

Funding

  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health

ASJC

  • Medicine(all)

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