Ontogeny of T cell development in avian scleroderma

Area of Science:

• Immunology
• Developmental Biology
• Avian Pathology

Background:

• UCD line 200 chickens exhibit inherited fibrotic disease, antinuclear antibodies, and collagen antibodies.
• Early skin lesions show significant T lymphocyte infiltration, suggesting an immune-mediated process.
• The study investigates if T lymphocyte differentiation abnormalities predispose these chickens to autoimmune disease.

Purpose of the Study:

• To investigate the hypothesis that developmental abnormalities in T lymphocyte differentiation contribute to autoimmune disease in UCD line 200 chickens.
• To analyze the thymic microenvironment and T cell function during ontogeny in these birds.
• To identify specific defects in T cell development that may lead to autoimmunity.

Main Methods:

• Analysis of thymic microenvironment using monoclonal antibodies against stromal cell subsets and MHC determinants.
• Assessment of T-cell graft-versus-host reactivity.
• Evaluation of T cell responses to mitogenic stimulation and interleukin-2 (IL-2) using flow cytometry (FACS).

Main Results:

• Line 200 chickens display profound thymic structural defects, including absence of type I epithelium and excessive MHC class II positive cells and B cells/macrophages.
• These thymic defects are present from the late embryonic period, preceding clinical disease.
• Thymocytes show increased IL-2 receptor density, while peripheral blood lymphocytes exhibit poor mitogenic and reduced IL-2 responses, but normal graft-versus-host reactivity.

Conclusions:

• UCD line 200 chickens have selective T-cell differentiation abnormalities originating from thymic defects.
• These abnormalities, present early in development, likely result from faulty thymic education.
• Faulty thymic education leads to an inappropriate response to self-antigens, predisposing to autoimmune disease.