It is well established that the infectious agent of
scrapie can replicate in the lymphoreticular system (LRS). However, the effects of removal of LRS target tissues on the pathogenesis of the
infection and the accumulation of disease-associated
prion protein (
PrP(d)) in LRS tissues on specific immune cell subsets are poorly understood aspects. To address these questions 16 ARQ/ARQ sheep were subcutaneously inoculated in the drainage area of the prefemoral lymph node with brain homogenate derived from Suffolk sheep naturally infected with
scrapie. Fourteen sheep were then subjected to either early (14-17 days post-inoculation [dpi]) or late (175-201 dpi)
lymphadenectomy and culled at preclinical or clinical stages of
infection. Neither late nor even early
lymphadenectomy prevented
infection or had any effect on the accumulation of
PrP(d) in the LRS or CNS suggesting a rapid organic dissemination of the infectious agent after inoculation. Lymph nodes from eight
scrapie inoculated sheep selected on the basis of the amount of
PrP(d) in their LRS tissues (negative, low or high) were examined for six different immune cell markers. The
PrP(d) negative lymph nodes from two sheep with no evidence of
scrapie infection showed lower numbers of cluster of determination (CD) 21 positive cells than
PrP(d) positive nodes, irrespective of their location (hind leg or head). However, quantitative differences in the expression of this marker were not detected when comparing lymph nodes with low and high levels of
PrP(d) accumulation, suggesting that proliferation of CD21 positive cells is related to
scrapie infection, but not directly linked to the magnitude of
PrP(d) accumulation. An additional observation of the study was that sheep that were methionin-
threonine at
codon 112 of the
prion protein gene showed lower attack rates than
methionine homozygotes (67% and 100%, respectively) and also generally lower levels of
PrP(d) accumulation in the LRS and brain and increased survival times, suggesting an influence of such polymorphism in the susceptibility to
scrapie.