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 in vivo 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+, CD8+, y8, 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+ and CD8+ 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+ 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+ cells,
confirming the importance of PMNs in the development of the DTH lesion.
The migratory ability of PMNs and CD4+ cells to the sites of dermally injected
proinflammatory mediators (IL-8, TNF-a, and zymosan activated plasma) was
subsequently shown to 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
Finally, the presence of cytokine mRNA (IL-10, TNF-a, IFN-y and IL2-R) in
the early lesions of both groups was assessed using reverse transcription polymerase
chain reaction (RT-PCR) technology. This indicated that the mRNA expression
pattern of these cytokines was not significantly different in control and MVV
In conclusion, the work has shown a significant depression of the DTH
response in sheep infected with MVV. This depression is associated with decreased
density of PMNs and CD4+ cells in the early reaction, but is not associated with
abnormalities in the trafficking of these cells to dermally injected proinflammatory
mediators, the presence of antibody/antigen complexes, the presence of viral RNA,
or difference in the cytokine mRNA production profile. The importance of the PMN
in the DTH has been indicated, and a defect in the in vivo immune response of the
PMN in MVV infected sheep has been described.