MRC Centre for Transplantation, King's College London, Guy's Hospital, London, UK.
West London Renal and Transplant Centre, Imperial College London and Imperial College NHS Trust, Hammersmith Hospital, London, UK.
Kidney Int. 2015 Sep;88(3):560-8. doi: 10.1038/ki.2015.100. Epub 2015 Apr 1.
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-γ 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.
我们探讨了 B 淋巴细胞如何影响抗体介导排斥反应（AMR）患者的体外 T 细胞同种反应，检测 B 细胞是否会优先参与这组患者。从 65 名接受活检的患者中采集外周血单核细胞：14 名 AMR 患者和 5 名无病理协议患者；38 名 AMR 患者和 8 名“因原因”而非免疫性损伤患者。使用酶联免疫斑点测定法，我们发现 65 名患者的 119 个总样本中有 45 个产生了间接同种识别的干扰素-γ。B 细胞优先在 AMR 患者的样本中处理和呈递供体同种抗原。在另外 25 个样本中，通过耗尽 CD25(+)细胞显示了 B 细胞依赖性同种特异性反应，这些个体的 CD4CD25hi 细胞比例更高。在 21 个样本中，通过耗尽 CD19(+)细胞显示了反应性，与 IgG/IgM 多克隆激活后向 IL-10 极化细胞因子产生相关。总体而言，这表明 AMR 患者体外间接供体特异性 T 细胞反应中 B 细胞有显著贡献。大约一半患者的 T 细胞或 B 细胞的不同表型的主动抑制表明，慢性 AMR 的特征不是免疫调节的普遍丧失。因此，分层方法可以适应细胞介导免疫的异质性，可能有利于治疗移植物功能障碍。
