B-lymphocytes support and regulate indirect T-cell alloreactivity in individual patients with chronic antibody-mediated rejection
B-lymphocytes support and regulate indirect T-cell alloreactivity in individual patients with chronic antibody-mediated rejection
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DOI：
10.1038/ki.2015.100
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发表时间：
2015-09-01
影响因子：
19.6
通讯作者：
Dorling, Anthony
中科院分区：
文献类型：
--
作者：
Shiu, Kin Y.;McLaughlin, Laura;Dorling, Anthony
我们探索了 B 淋巴细胞如何影响抗体介导的排斥 (AMR) 患者的体外 T 细胞同种异体反应，测试 B 细胞是否会优先参与这组患者。外周血单核细胞采集自 65 名进行活检的患者：14 名患者患有 AMR，5 名患者没有按照方案进行病理学检查； 38 例出现 AMR，8 例出现“有原因”的非免疫性损伤。使用酶联免疫吸附斑点测定，我们发现 65 名患者的 119 个样本中的 45 个通过间接同种异体识别产生了干扰素 γ。 B 细胞优先处理并呈递 AMR 患者样本中的供体同种抗原。在另外 25 个样本中，通过 CD25(+) 细胞的耗竭显示了 B 细胞依赖性同种异体特异性反应性，并且这些个体具有更高百分比的 CD4CD25hi 细胞。在 21 个样本中，CD19(+) 细胞的消耗显示了反应性，这与 IgG/IgM 多克隆激活后极化细胞因子产生向 IL-10 相关。总体而言，这表明 B 细胞对 AMR 患者体外间接供体特异性 T 细胞反应有显着贡献。大约一半患者的 T 细胞或 B 细胞不同表型的主动抑制表明，慢性 AMR 并不以免疫调节普遍丧失为特征。因此，适应细胞介导免疫异质性的分层方法可能有利于治疗移植物功能障碍。
We explored how B-lymphocytes influence in vitro T-cell alloresponses in patients with antibody-mediated rejection (AMR), testing whether B-cells would be preferentially involved in this group of patients. Peripheral blood mononuclear cells were collected from 65 patients having biopsy: 14 patients with AMR and 5 with no pathology on protocol; 38 with AMR and 8 with nonimmunologic damage on 'for cause'. Using enzyme-linked immunosorbent spot assays, we found interferon-gamma production by indirect allorecognition in 45 of 119 total samples from the 65 patients. B-cells preferentially processed and presented donor alloantigens in samples from AMR patients. In a further 25 samples, B-cell-dependent allo-specific reactivity was shown by depletion of CD25(+) cells and these individuals had higher percentages of CD4CD25hi cells. In 21 samples, reactivity was shown by depletion of CD19(+) cells, associated with polarized cytokine production toward IL-10 after polyclonal activation by IgG/IgM. Overall, this shows a significant contribution by B-cells to indirect donor-specific T-cell reactivity in vitro in patients with AMR. Active suppression by distinct phenotypes of T- or B-cells in approximately half of the patients indicates that chronic AMR is not characterized by a universal loss of immune regulation. Thus, stratified approaches that accommodate the heterogeneity of cell-mediated immunity might be beneficial to treat graft dysfunction.