Submitted to: Veterinary Immunology and Immunopathology
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 3/25/2010
Publication Date: 8/15/2010
Publication URL: www.sciencedirect.com/science?_ob=MImg&_imagekey=B6TD5-4YRPDK9-2-5&_cdi=5189&_user=7810834&_pii=S0165242710001121&_orig=search&_coverDate=04%2F01%2F2010&_sk=999999999&view=c&wchp=dGLbVlW-zSkzS&md5=938a6e502325c40f94527fffc5c7b103&ie=/sdarticle.pdf
Citation: Nelson, D.D., Davis, W.C., Brown, W.C., Li, H., O'Toole, D., Oaks, J.L. 2010. CD8+/perforin+/WC1- gammadelta T cells, CD8+ alphabeta T cells, infiltrate vasculitis lesions of American bison (Bison bison) with experimental sheep-associated malignant catarrhal fever. Veterinary Immunology and Immunopathology. 136(3-4):284-291. Interpretive Summary: Sheep-associated malignant catarrhal fever (SA-MCF) is a fatal disease that poses a significant threat to American bison, as well as cattle. The disease is caused by a herpesvirus called ovine herpesvirus 2 and one of the typical lesions in the diseased animals is lymphocytic vasculitis, inflammation of blood vessels infiltrated with lymphocytes (immune cells) . Little is known about the vasculitis, and limited information is available about what types of lymphocytes are involved in the vascular lesions in the clinically affected animals with SA-MCF. By clarifying the immunophenotype of lymphocytes in vascular lesions, we can better understand the disease and develop effective control strategies. In this study we analyzed tissues with vascular lesions from six experimentally infected bison using multi-color fluorescent techniques. The study definitively defined what immune cell types are persistently in the vascular lesions. The findings suggest that these cells have the potential for cell killing and/or regulatory function and may contribute to the development of vasculitis in MCF. Results of the study support the previous suggestions that MCF is fundamentally a disease of immune dysregulation.
Technical Abstract: Sheep-associated malignant catarrhal fever (SA-MCF) caused by ovine herpesvirus-2 (OvHV-2) 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 disease. The pathogenesis of vasculitis 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 CD8+ and CD3+ cells predominate within vascular lesions in the brains of bison. The CD8+ cells detected in the vascular lesions of cattle and bison were assumed to be cytotoxic aß T lymphocytes since WC1+ 'd cells were not identified. However, the previously identified CD8+ lymphocytes could be either aß T cells, 'd T cells, and/or NK cells. By clarifying the immunophenotype of lymphocytes in vascular lesions, we can better understand the pathogenesis of vasculitis in SA-MCF. Six captive bison were infected by nasal aerosolization with OvHV-2 from sheep nasal secretions. Polychromatic immunophenotyping analyses determined that CD8+/perforin+ 'd T cells, CD4+/perforin- aß T cells, and B cells consistently infiltrated vascular lesions in the urinary bladder, kidney, and liver of all six bison. CD8+ aß T cells, NK cells (NKp46 +), macrophages (CD14+ or calprotectin+ cells), and WC1+ 'd T cell positive cells were not consistently identified. CD8+/perforin+/WC1- 'd T and CD4+/perforin- aß T cells have the potential for cytotoxicity and/or regulatory function, and both may contribute to the pathogenesis of MCF. Results of the present study support the previous suggestions that MCF is fundamentally a disease of immune dysregulation.