Quantitative analysis of infiltrating immune cells and bovine papillomavirus type 1 E2-positive cells in equine sarcoids

Abstract

Sarcoids are the most frequently observed skin tumours in equids and consist of cutaneous accumulations of transformed fibroblasts. Their aetiopathogenesis is closely linked to a presumably abortive infection by bovine papillomavirus (BPV) types 1 and 2. In cattle, dermal fibropapillomas induced by BPV1/2 usually regress spontaneously due to a local, cell-mediated, immune response; however, equids appear to lack an effective immune response to BPV1/2 and mechanisms of immune evasion have been postulated. As a consequence, equine sarcoids tend to persist and are prone to recur. In this study, cryosections were analysed by immunofluorescent staining and a high content analysis system to determine the presence and distribution of CD4+, CD8+, FoxP3+, RORγt−, CD206+ and CD14+ cells, along with expression of the BPV1 early regulatory protein E2. A higher density of cells was positive for BPV1 E2+ within the transformed tissue than in perilesional tissue or normal skin of horses with sarcoids and control horses. The proportion of CD8+ cytotoxic T cells was significantly increased in perilesional and lesional tissues, whereas CD4+ T helper cells were present in higher density only in lesional tissue compared to normal skin from horses with and without sarcoids. The proportion of pro-inflammatory CD4+FoxP3+RORγt+ regulatory T cells was decreased in sarcoid tissue compared to perilesional, distant and control tissue. There were no significant differences in densities of CD4+FoxP3+ RORγt− regulatory T cells between sarcoids and control tissues. Equine sarcoids are characterised by infiltrations of CD8+ and CD4+ T cells, with decreased representation by pro-inflammatory CD4+FoxP3+RORγt+ regulatory T cells.