CD8+/perforin+/WC1− γδ T cells, not CD8+ αβ T cells, infiltrate vasculitis lesions of American bison (Bison bison) with experimental sheep-associated malignant catarrhal fever

Sheep-associated malignant catarrhal fever (SA-MCF) caused by ovine herpesvirus-2 (OvHV-2), a γ-herpesvirus in the Macavirus genus, is a fatal disease associated with lymphoproliferation, lymphocytic vasculitis, and mucosal ulceration in clinically susceptible species. SA-MCF is an important threat to American bison (Bison bison) due to their high susceptibility to this disease. Currently, the pathogenesis of disease in SA-MCF is poorly understood, and the immunophenotype of lymphocytes that infiltrate the vascular lesions of bison and cattle with SA-MCF has been only partially defined. Previous single-color immunohistochemistry studies have demonstrated that CD8+ cells and CD4+ cells predominate within vascular infiltrates in cattle and bison. The CD8+ cells detected in the vascular lesions of cattle and bison were assumed to be cytotoxic αβ T lymphocytes. However, polychromatic immunophenotyping analyses in this study showed that CD8+/perforin+ γδ T cells, CD4+/perforin− αβ T cells, and B cells infiltrate vascular lesions in the urinary bladder, kidney, and liver of six bison with experimentally-induced SA-MCF. CD8+ αβ T cells and WC1+ γδ T cell cells were only infrequently and inconsistently identified. This study confirmed our hypothesis that the predominant CD8+ lymphocytes infiltrating the vascular lesions of bison with SA-MCF are cytotoxic lymphocytes of the innate immune system, not CD8+ αβ T cells. Results of the present study support the previous suggestions that MCF is fundamentally a disease of immune dysregulation.