In Situ Characterization of Mononuclear Leukocytes in Skin and Digestive Tract of Persistently Bovine Viral Diarrhea Virus-infected Clinically Healthy Calves and Calves with Mucosal Disease

Abstract

The phenotypic identity of mononuclear leukocytes in skin and digestive tract of bovine viral diarrhea virus (BVDV)-infected animals was examined using sensitive single and double labeling immunocyto-chemical techniques. Occurrence and distribution of B lymphocytes, T lymphocytes of either the helper (BoT4) or suppressor/cytotoxic (BoT8) subsets, and macrophages (M⊘) were examined. No differences were found in the skin and digestive tract of persistently infected clinically healthy calves and uninfected controls, despite widespread virus-antigen presence in keratinocytes (stratum basale and stratum spinosum) of skin and upper digestive tract, in dermal/subepithelial macrophages (M⊘), in gut-epithelial cells, and in lymphocytes and M⊘/monocytes of blood and lymphoid tissues of the former group. M⊘ and Langerhans cells (LC) were the prevailing leukocyte types in the keratinized epithelia and subepithelial connective tissues, with occasional T lymphocytes (mostly intraepithelially located and of the BoT8 phenotype). No B cells were seen. Some infiltrating leukocytes also contained virus antigen. In animals succumbing to mucosal disease (MD), hyper- and parakeratotic changes, as well as necrotizing epithelial lesions, were accompanied by massive infiltration in dermis and epithelium of major histocompatibility complex (MHC) class II antigen positive cells (M⊘ and LC), some T lymphocytes (predominantly BoT8 positive cells), and, only rarely, B cells. M⊘ also predominated in lamina propria of the gastrointestinal tract. Findings suggest that M⊘ activation is an important aspect of MD pathogenesis. In contrast, the contention that T lymphocytes may play a major role could not be substantiated.