Enhanced expression of LAG-3 on lymphocyte subpopulations from persistently lymphocytotic cattle infected with bovine leukemia virus
Enhanced expression of LAG-3 on lymphocyte subpopulations from persistently lymphocytotic cattle infected with bovine leukemia virus
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DOI：
10.1016/j.cimid.2012.09.005
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发表时间：
2013-01-01
影响因子：
2
通讯作者：
Ohashi, Kazuhiko
中科院分区：
文献类型：
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作者：
Konnai, Satoru;Suzuki, Saori;Ohashi, Kazuhiko
淋巴细胞激活基因 3 (LAG-3) 是一种免疫抑制性受体，主要在 T 细胞中表达，参与多种引起慢性感染和肿瘤的病原体的免疫逃避。然而，与人类或小鼠 LAG-3 不同，LAG-3 在家畜中的功能分析尚未见报道。因此，在本研究中，分析了牛白血病病毒 (BLV) 感染的牛中的牛 LAG-3 表达。在持续性淋巴细胞（PL）牛中，LAG-3（+）CD4（+）细胞和LAG-3（+）CD8（+）细胞的数量得以保留，而MHC II+类细胞的数量明显高于对照动物。相反，与对照牛和无症状 (AL) 牛相比，PL 牛 PBMC 上 LAG-3 的平均荧光强度 (MFI) 显着增加。具体而言，来自 PL 牛的 CD4(+) 和 CD8(+) T 细胞的 LAG-3 表达水平显着增加。 LAG-3 表达与受感染动物中淋巴细胞和 MHC II+ 类细胞数量的增加呈正相关。 PD-L1 和 LAG-3 阻断测定的初步结果表明，通过添加抗 PD-L1 和 LAG-3 抗体，来自 PL 牛的 PBMC 中的 IFN-γ 和 IL-2 表达显着上调。这些发现表明，在 BLV 感染期间，LAG-3 可能通过其与 MHC II 类分子的结合和信号传导参与 T 细胞功能的抑制。 (c) 2012 Elsevier Ltd. 保留所有权利。
An immunoinhibitory receptor, lymphocyte activation gene-3 (LAG-3), which is mainly expressed in T-cells, is involved in the immune evasion of several pathogens causing chronic infections and tumors. However, unlike human or mouse LAG-3, no functional analysis of LAG-3 has been reported in domestic animals. Thus, in this study, bovine LAG-3 expression was analyzed in bovine leukemia virus (BLV)-infected cattle. In persistent lymphocytotic (PL) cattle, the numbers of LAG-3(+)CD4(+) cells and LAG-3(+)CD8(+) cells were conserved whilst the number of MHC class II+ cells was remarkably higher than in the control animals. In contrast, the mean fluorescence intensity (MFI) for LAG-3 on PBMCs from PL cattle was significantly increased compared to control and asymptomatic (AL) cattle. Specifically, the LAG-3 expression level was significantly increased in both CD4(+) and CD8(+) T cells from PL cattle. LAG-3 expression correlated positively with increased numbers of lymphocytes and MHC class II+ cells in infected animals. Preliminary results from PD-L1 and LAG-3 blockade assay revealed that IFN-gamma and IL-2 expressions were significantly up-regulated by addition of anti- PD-L1 and LAG-3 antibodies in PBMCs from PL cattle. These findings suggest that LAG-3 might be involved in the inhibition of T-cell function through its binding and signaling on MHC class II molecule during BLV infection. (c) 2012 Elsevier Ltd. All rights reserved.