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Title: The pathogenesis of natural and experimental arthropathies of sheep
Author: Anderson, A. A.
Awarding Body: University of Edinburgh
Current Institution: University of Edinburgh
Date of Award: 1995
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The pathogenesis of natural and experimental arthropathies in sheep is poorly understood. The aims of the work described in this thesis were: 1) to determine the expression of immunologically relevant molecules in synovial tissues from sheep at different stages of development from the foetus to the adult, and sheep infected with Maedi-Visna virus (MVV), a non-oncogenic retrovirus: 2) study the kinetics of inflammatory cell turnover in synovial tissues and trafficking into the draining lymph node in sheep with experimental antigen-induced arthritis (AIA). Immunohistological analysis of the synovial lining and flow cytometric analysis of cells in synovial fluid (SF) from sheep of different ages showed that there was a significant increase in the proportion of cells expressing MHC class II antigens during the first few months of life. Very few lymphoid cells were found in tissues from sheep of any age. Immunopathological studies of synovial tissues from clinically arthritic MVV-infected sheep showed that the inflammatory infiltrate was characterised by large numbers of large mononuclear cells and T lymphocytes, of which the CD8+ subset predominated over CD4+ and γδ T lymphocyte subsets. Large numbers of cells in the synovial lining expressed MHC class II and CD1 antigens. CD8+ T lymphocytes were found at a significantly higher density in some synovial tissues from MVV-infected sheep with no clinical signs of arthritis compared to tissues from control sheep. Additionally, the proportion of MHC class II-expressing cells in the subintima of these tissues was significantly higher than in tissues from control sheep. To characterise the progression of an inflammatory arthritis in a more controlled way, an AIA was generated in a group of adult sheep. Immunopathological studies of synovial tissues from sheep at defined time points following generation of arthritis showed that there were temporal differences in the proportions of individual cell types infiltrating these tissues. The CD4:CD8 T lymphocyte ratio was significantly higher, and the T:B and αβ:γδ T lymphocyte ratios were significantly lower in tissues from day 3 compared to day 30 following generation of arthritis. A large proportion of all three T lymphocyte subsets in SF were activated as judged by MHC class II and IL2 receptor expression. There was also temporal variation in the expression of some cell adhesion molecules by T lymphocytes in SF.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available