Immunological differences between susceptible and resistant sheep during the preclinical phase of scrapie infection

In order to investigate the relationship between the immune response to scrapie infection and genetic susceptibility to the disease in sheep, immune cell subsets and prion protein (PrP) expression were determined in susceptible and resistant Suffolk sheep in the preclinical phase of infection. At 6 months of age, 12 ARQ/ARQ (susceptible) and nine ARR/ARR (resistant) scrapie-free Suffolk lambs were challenged subcutaneously with scrapie inoculum. Prefemoral lymphadenectomies were carried out at 14 and 180 days post-inoculation (p.i.) and serial bleeds were collected at monthly intervals for up to 1 year p.i. An indirect double-labelling procedure was carried out on peripheral blood mononuclear cells (PBMCs) and lymph node cell preparations and analysed using flow cytometry. Prior to scrapie challenge, significantly more PrP(+) cells were detected in PBMCs from the susceptible sheep. Furthermore, following challenge, significantly more CD8(+) and gammadelta(+) T cells were detected in the PBMCs of the resistant sheep. However, at both 14 and 180 days p.i, CD21(+) cell expression was significantly higher in the lymph node preparations of the susceptible sheep. In contrast, more CD4(+) cells were detected in the lymph nodes of the resistant sheep at both time points. It was concluded that significant differences in immune cell subsets and PrP expression occur between ARQ/ARQ and ARR/ARR Suffolk sheep in the preclinical phase of infection.