PD-1 function in apoptosis of T lymphocytes in canine visceral leishmaniasis
PD-1 function in apoptosis of T lymphocytes in canine visceral leishmaniasis
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DOI：
10.1016/j.imbio.2016.03.007
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发表时间：
2016-08-01
期刊：
影响因子：
2.8
通讯作者：
Felix de Lima, Valeria Marcal
中科院分区：
文献类型：
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作者：
Chiku, Vanessa Marim;Oliveira Silva, Kathlenn Liezbeth;Felix de Lima, Valeria Marcal
感染婴儿利什曼原虫的狗的T淋巴细胞数量减少。PD-1（程序性细胞死亡1）是由免疫细胞表达的B7-CD 28家族的新成员，其与PD-L1（CD 274）或PD-L2（CD 273）的结合诱导T细胞的失活或凋亡。本研究旨在评估PD-1及其配体的表达，以及阻断诱导T淋巴细胞凋亡，PBMC和脾脏白细胞产生TNF-α，IL-4和一氧化氮，以及内脏利什曼病（VL）犬的寄生虫负荷。结果表明，VL犬外周血CD 3（+）T细胞和CD 21（+）B淋巴细胞及脾脏单个核细胞中PD 1及其配体的表达增加。在外周血单核细胞中，仅PD-1配体表现出表达增加;然而，在脾巨噬细胞中，观察到PD-1及其配体的表达增加。与健康犬相比，VL犬外周血和脾脏T淋巴细胞的凋亡水平较高。在外周血和脾脏单核细胞培养物中阻断PD-1及其配体的单克隆抗体可减少CD 3（+）T淋巴细胞凋亡的数量。在用针对PD-1的阻断性单克隆抗体处理的外周血单核细胞的培养上清液中，一氧化氮、TNF-α和IL-4的浓度增加。在用阻断PD-1及其配体的抗体进行所有处理后，脾细胞的培养上清液中TNF-α浓度增加;然而，IL-4的量仅在存在PD-1阻断剂的情况下增加。在VL犬的单核外周血中使用PD-1阻断单克隆抗体治疗可降低寄生虫负荷，同时增加TNF-α。我们的结论是，在犬内脏利什曼病，PD-1及其配体参与诱导T淋巴细胞凋亡和调节一氧化氮，TNF-α和IL-4的产生，以及寄生虫负荷。(C)2016年爱思唯尔有限公司。All rights reserved.
Dogs infected with Leishmania infantum have a reduced number of T lymphocytes. PD-1 (Programmed cell death 1) a new member of the B7-CD28 family that is expressed by immune cells, and its binding to PD-Ll (CD274) or PD-L2 (CD273) induces the deactivation or apoptosis of T cells. This study aimed to evaluate the expression of PD-1 and its ligands, as well as blocking in the induction of apoptosis in T lymphocytes, TNF-alpha, IL-4 and nitric oxide production by leucokocytes from PBMC and spleen and the parasite load in dogs with visceral leishmaniasis (VL). Our results showed that the expression of PD1 and its ligands was increased in CD3(+) T cells and CD21(+) B lymphocytes within the peripheral blood and splenic mononuclear cells of dogs with VL. In peripheral blood monocytes, only PD-1 ligands exhibited increased expression; however, in spleen macrophages, increased expression of both PD-1 and its ligands was observed. Levels of apoptosis in peripheral blood and splenic T lymphocytes were higher in dogs with VL compared to healthy dogs. Blocking monoclonal antibodies to PD-1 and its ligands in the culture of mononuclear cells from the peripheral blood and spleen decreased the amount of CD3(+) T lymphocyte apoptosis. The concentration of nitric oxide, TNF-alpha and IL-4 increased in the culture supernatants of peripheral blood mononuclear cells treated with a blocking monoclonal antibody against PD-1. The TNF-alpha concentration increased in the culture supernatants of splenic cells following all treatments with antibodies blocking PD-1 and its ligands; however, the amount of IL-4 increased only in the presence of a PD-1 blocking agent. Treatment with a PD-1 blocking monoclonal antibody in the mononuclear peripheral blood of dogs with VL reduced the parasite burden while increased TNF-alpha. We conclude that in canine visceral leishmaniasis, PD-1 and its ligands are involved in the induction of T lymphocyte apoptosis and in regulating the production of nitric oxide, TNF-alpha, and IL-4, as well as the parasitic load. (C) 2016 Elsevier GmbH. All rights reserved.