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)
Immunohistlogical 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 fife. 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 y5 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 MW-infected
sheep with no clinical signs of arthritis compared to tissues from control sheep. Additionally, the
proportion of MHC class Il-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 the T:B and afkyS 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.
The feasibility of following inflammatory cell trafficking out of inflamed joints into the afferent
lymphatics was assessed using the AIA model. Following cannulation of the popliteal pseudoafferent
lymphatic duct in the hindlimb, AIA was generated in the tibiotarsal joint distal to the cannulation site.
In a small number of sheep it was possible to monitor changes in the draining lymph following
generation of arthritis or a flare reaction. In the acute stages of arthritis these changes were
characterised by large numbers of neutrophils followed by increases in the concentration or output of
lymphocytes and dendritic cells (DC). Temporal variation was observed in the expression of activation
and other molecules by lymphocytes and DC in the draining lymph. Antigen uptake by different cell
types in AL was demonstrated by generating arthritis using fluorescein-labelled antigen and the potential
for DC to migrate from SF into the afferent lymphatics was investigated using DC labelled in vitro with
a fluorescent dye. These results indicate that lymphatic cannulation could provide an important novel
approach to studying the dynamics of the inflammatory process in joints.