Department of Disease Control, Graduate School of Veterinary Medicine, Hokkaido University, Sapporo, Japan.
Microbiol Immunol. 2010 May;54(5):291-8. doi: 10.1111/j.1348-0421.2010.00208.x.
Recent work has shown that PD-1, an immune inhibitory receptor, is involved in mechanisms for down-regulating immune responses during tumor progression or chronic viral infection. However, in the case of bovine diseases, there have been no reports on this molecule due to lack of information about bovine PD-1. In this study, we performed identification and preliminary characterization of the bovine PD-1 gene in two breeds of cattle. We cloned full cDNA sequences encoding for PD-1 from both Holstein-Friesian and Japanese Black breeds, and found that both of the genes encoded a 282-amino acid protein, which had a signal sequence, transmembrane domain and an immunoreceptor tyrosine-based inhibitory motif. This bovine PD-1 showed 72.9% and 65.6% homology to human and mouse PD-1, respectively, both of which have been well characterized and documented. Quantitative real-time PCR analysis showed that bovine PD-1 is expressed predominantly in T-cells (such as CD4(+) and CD8(+) cells) and among PBMCs, and is strongly upregulated on T-cell stimulation via ConA. A limited number of cattle were tested yet, as expected, the degree of PD-1 mRNA expression in CD4(+) and CD8(+) T-cells was greater in cattle with bovine leukemia virus-induced lymphoma than in uninfected cattle. Further studies to characterize the functions of bovine PD-1 are therefore warranted, in order to elucidate the mechanism of the immunosuppression associated with progression of several diseases and therapy in cattle.
最近的研究表明，PD-1 是一种免疫抑制受体，参与肿瘤进展或慢性病毒感染期间的免疫反应下调机制。然而，在牛病方面，由于缺乏牛 PD-1 的信息，尚未有关于该分子的报道。在这项研究中，我们在两个牛品种中鉴定并初步表征了牛 PD-1 基因。我们从荷斯坦-弗里森和日本黑牛品种克隆了 PD-1 的全长 cDNA 序列，并发现这两个基因都编码了一个 282 个氨基酸的蛋白质，它具有信号序列、跨膜结构域和免疫受体酪氨酸抑制基序。这种牛 PD-1 与人类和小鼠 PD-1 的同源性分别为 72.9%和 65.6%，这两个分子都得到了很好的表征和研究。实时定量 PCR 分析表明，牛 PD-1 主要在 T 细胞（如 CD4(+)和 CD8(+)细胞）和 PBMCs 中表达，并且在 T 细胞通过 ConA 刺激时强烈上调。由于检测的牛数量有限，与预期的一样，在感染牛白血病病毒诱导的淋巴瘤的牛中，CD4(+)和 CD8(+)T 细胞中 PD-1 mRNA 的表达程度高于未感染的牛。因此，有必要进一步研究牛 PD-1 的功能，以阐明与几种疾病进展和牛治疗相关的免疫抑制机制。
