Blockade of bovine PD-1 increases T cell function and inhibits bovine leukemia virus expression in B cells in vitro.
Blockade of bovine PD-1 increases T cell function and inhibits bovine leukemia virus expression in B cells in vitro.
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DOI：
10.1186/1297-9716-44-59
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发表时间：
2013-07-22
影响因子：
4.4
通讯作者：
Ohashi K
中科院分区：
文献类型：
--
作者：
Ikebuchi R;Konnai S;Okagawa T;Yokoyama K;Nakajima C;Suzuki Y;Murata S;Ohashi K
程序性死亡-1（PD-1）是一种已知的免疫抑制受体，有助于免疫逃避各种肿瘤细胞和病原体引起的慢性感染，如牛白血病病毒（BLV）感染。首先，在本研究中，为了建立牛PD-1的表达和功能分析方法，建立了产生牛PD-1特异性单克隆抗体（mAb）的杂交瘤。用这些抗PD-1 mAb处理增强了牛外周血单核细胞（PBMC）的干扰素-γ（IFN-γ）产生。接下来，为了检查通过抗PD-1 mAb阻断PD-1是否可以上调慢性感染期间的免疫反应，使用抗PD-1 mAb进行了从患有或不患有淋巴瘤的BLV感染牛分离的PBMC中PD-1的表达和功能分析。BLV感染牛淋巴瘤组血液和淋巴结中PD-1+ CD 4 + T细胞和淋巴结中PD-1+ CD 8 + T细胞的频率均高于未感染牛和未感染牛。在BLV感染牛的PBMC中，PD-1阻断剂增强了IFN-γ的产生和增殖，并降低了BLV-gp 51表达和B细胞活化，以响应BLV-gp 51肽混合物。这些数据表明，抗牛PD-1 mAb可以通过上调免疫应答来提供控制BLV感染的新疗法。
Programmed death-1 (PD-1) is a known immunoinhibitory receptor that contributes to immune evasion of various tumor cells and pathogens causing chronic infection, such as bovine leukemia virus (BLV) infection. First, in this study, to establish a method for the expression and functional analysis of bovine PD-1, hybridomas producing monoclonal antibodies (mAb) specific for bovine PD-1 were established. Treatment with these anti-PD-1 mAb enhanced interferon-gamma (IFN-γ) production of bovine peripheral blood mononuclear cells (PBMC). Next, to examine whether PD-1 blockade by anti-PD-1 mAb could upregulate the immune reaction during chronic infection, the expression and functional analysis of PD-1 in PBMC isolated from BLV-infected cattle with or without lymphoma were performed using anti-PD-1 mAb. The frequencies of both PD-1+ CD4+ T cells in blood and lymph node and PD-1+ CD8+ T cells in lymph node were higher in BLV-infected cattle with lymphoma than those without lymphoma or control uninfected cattle. PD-1 blockade enhanced IFN-γ production and proliferation and reduced BLV-gp51 expression and B-cell activation in PBMC from BLV-infected cattle in response to BLV-gp51 peptide mixture. These data show that anti-bovine PD-1 mAb could provide a new therapy to control BLV infection via upregulation of immune response.
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影响因子：
3.9
作者：
Jeon, Dae-Hyun;Oh, Keunhee;Lee, Gene
通讯作者：
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影响因子：
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作者：
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DOI：
10.1073/pnas.1003345107
发表时间：
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影响因子：
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作者：
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