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

机译:马肉瘤中浸润性免疫细胞和牛乳头瘤病毒1型E2阳性细胞的定量分析

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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(+), ROR gamma t(-), 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(+)ROR gamma t(+) 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(+)ROR gamma t(-) 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(+)ROR gamma t(+) regulatory T cells. (C) 2016 Elsevier Ltd. All rights reserved.
机译:结节病是最常观察到的皮肤肿瘤,由转化成纤维细胞的皮肤积聚组成。它们的致病机理与1型和2型牛乳头瘤病毒(BPV)可能引起的流产感染密切相关。但是,马匹似乎缺乏对BPV1 / 2的有效免疫反应,并且已经提出了逃避免疫的机制。结果,马类肌瘤倾向于持续存在并易于复发。在这项研究中,冷冻切片通过免疫荧光染色和高含量分析系统进行分析,以确定CD4(+),CD8(+),FoxP3(+),RORγt(-),CD206(+)和CD14(+)细胞,以及BPV1早期调节蛋白E2的表达。与肉瘤和对照马相比,转化后的组织中BPV1 E2(+)的细胞密度更高,高于病灶周围组织或正常皮肤中的BPV1 E2(+)。与有或没有肉瘤的马的正常皮肤相比,在病变和病变组织中CD8(+)细胞毒性T细胞的比例显着增加,而CD4 + T辅助细胞仅在病变组织中以更高的密度存在。与周围,远处和对照组织相比,结节组织中促炎性CD4(+)FoxP3(+)RORγt(+)调节性T细胞的比例降低。在结节状组织和对照组织之间,CD4(+)FoxP3(+)RORγt(-)调节性T细胞的密度没有显着差异。马类肉瘤的特征是CD8(+)和CD4(+)T细胞的浸润,而促炎性CD4(+)FoxP3(+)RORγt(+)调节性T细胞的代表性下降。 (C)2016 Elsevier Ltd.保留所有权利。

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