Experimental mucosal disease of cattle: changes in cell proliferation in lymphoid tissues and intestinal epithelium

In mucosal disease of cattle, the initial and most severe lesions are found in the lymphoid follicles and intestinal crypts, both sites showing a high cell proliferation rate. In the present study, the changes in the number and distribution of proliferating cells were investigated immunohistologically, by demonstrating the proliferation-associated nuclear antigen, Ki-67. Tissues were obtained from 30 cattle, all of which had a persistent natural infection with non-cytopathogenic (ncp) bovine virus diarrhoea virus (BVDV), and 22 of which were subsequently inoculated with antigenically closely related strains of cytopathogenic (cp) BVDV to produce mucosal disease (MD); the remaining eight cattle served as uninoculated controls. Twelve of the inoculated cattle were killed before the onset of clinical signs of MD ("early phase"), and 10 when they were moribund ("late phase"). In the controls, the lymphoid follicles in lymph nodes and Peyer's patches consisted predominantly of Ki-67-positive cells; high numbers of such cells were observed in the crypts of the small intestine and moderate numbers in the crypts of the large intestine. In the early phase of MD, the number of Ki-67-positive cells in the lymphoid follicles and in the domes of the Peyer's patches gradually decreased; but in the mucosa, foci of crypts with increased numbers of Ki-67-positive cells were observed. In the late phase of MD, only a few Ki-67-positive cells were present in the lymphoid follicles. There was an increase in the number of Ki-67-positive cells in most crypts in the small and large intestine, but foci of crypts without Ki-67-positive cells occurred.