| Summary: | Maedi Visna virus (MVV) is the prototype lentivirus, capable of infecting cells of the monocyte/macrophage series in sheep. Infection is associated with pathological changes characterised by dysfunction of the cell mediated immune system. The work described in this thesis was undertaken to study <I>in vivo</I> cell mediated immune function in sheep infected with MVV using the tuberculin driven delayed type hypersensitivity (DTH) reaction as the experimental system. The gross and immunohistological characteristics of the DTH were firstly evaluated in control sheep (CD4<SUP>+</SUP>, CD8<SUP>+</SUP>, γδ, and B lymphocytes, macrophages and MHC class II expression). Grossly, the reaction consisted of an indurative plaque, maximal in size at 48-72 hours post challenge. Histologically, there was an early infiltrate of polymorphonuclear neutrophils (PMNs), with a subsequent influx of CD4<SUP>+</SUP> and CD8<SUP>+</SUP> T cells. Macrophages and MHC class II bearing cells left the lesion at the later stages. In comparison, MVV infected sheep exhibited a reduction in the size of the gross DTH which was significantly associated with a decreased density of PMNs and CD4<SUP>+</SUP> cells in the early reaction, but not with the degree of classical pathological change evaluated at subsequent post mortem or the presence of viral RNA in the skin. Depletion of circulating PMNs using cytotoxic drugs in control sheep resulted in the depression in the size of the DTH and a reduced influx of CD4<SUP>+</SUP> cells, confirming the importance of PMNs in the development of the DTH lesion. The migratory ability of PMNs and CD4<SUP>+</SUP> cells to the sites of dermally injected proinflammatory mediators (IL-8, TNF-α, and zymosan activated plasma) was subsequently shown to be similar in control and MVV infected sheep. Evaluation of the levels of circulating anti-PPD antibodies in the MVV infected and control groups provided evidence for a negative association between antibody levels and DTH size suggesting a switch to a Th2 type response in the MVV infected sheep.
|
|---|
