Characterization of immune responses during regression of rabbit oral papillomavirus infections

Rabbit oral papillomavirus (ROPV) is a mucosatropic papillomavirus that causes small benign discrete papillomas within the oral cavity of domestic rabbits. The goal of this study was to characterize the immune cell infiltrate over the course of regression of oral papillomas. ROPV-infected oral tissues were harvested at various time points after infection and analyzed by immunohistochemistry for papilloma morphology, viral capsid proteins, and associated immune infiltrates. The results of this study indicated that the L1 and L2 viral capsid proteins were lost rapidly at a time that coincided with an inflammatory response from the rabbit. This inflammatory response began with a rapid rise in numbers of CD11c⁺ cells at early regression. CD11c ⁺ cells continued to increase in frequency through mid-regression and remained the most-represented cell through late regression. The initial rise in CD11c⁺ cells was followed by an infiltrate containing increased numbers of activated T cells, including CD4⁺ and CD25⁺ cells, during mid-regression. Mid-regression coincided spatially with a loss of viral capsid stain, suggesting that immune cells or cytokines or both were playing a key role in clearance of the papillomas. CD8⁺ cells increased at the lowest rate and were at low levels in the papilloma epidermis even at mid-regression. All cell types decreased by late regression. CD11c ⁺ and major histocompatibility class II⁺ cells were the last populations of cells to decrease in number.