Impact of Induction Therapy on Circulating T Follicular Helper Cells and Subsequent Donor-Specific Antibody Formation After Kidney Transplant
Impact of Induction Therapy on Circulating T Follicular Helper Cells and Subsequent Donor-Specific Antibody Formation After Kidney Transplant
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DOI：
10.1016/j.ekir.2018.11.020
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发表时间：
2019-03-01
影响因子：
6
通讯作者：
Metes, Diana
中科院分区：
文献类型：
--
作者：
Macedo, Camila;Hadi, Kevin;Metes, Diana
简介：肾移植 (KTx) 后有助于生成供体特异性抗 HLA 抗体 (DSA) 的细胞事件尚不清楚。这种机制的表征可以允许定制免疫抑制以造福于敏感患者。方法：我们前瞻性地监测了从 KTx 前到 KTx 后 1 年接受 T 细胞耗竭（胸腺球蛋白，n = 54）或 T 细胞非耗竭（巴利昔单抗，n = 20）诱导治疗的 KTx 受者的循环 T 滤泡辅助细胞 (cT(FH)) 细胞，并评估了它们的情况。除了健康对照 (n = 13) 之外，还对总共 307 份血液样本进行了由于诱导和 DSA 发生而导致的表型变化。结果：在 KTx 之前，患者表现出与健康对照相似的静息中枢记忆 cT(FH) 细胞水平相当的水平。与巴利昔单抗诱导不同，胸腺球蛋白诱导显着耗尽 cT(FH) 细胞，触发淋巴细胞减少诱导的增殖，使 cT(FH) 细胞偏向增加 Th1 极化、效应记忆和升高程序性细胞死亡蛋白 1 (PD-1)(int/hi) 表达，类似于激活的表型。无论诱导如何，在 KTx 后发生 DSA 的患者都含有 KTx 前供体反应性记忆白细胞介素 (IL)-21(+) cT(FH) 细胞，并且在 KTx 后表现出较高的 cT(FH) 百分比和较低的 T 调节性 (T-REG) 细胞百分比，导致 DSA 发生时 cT(FH):T-REG 比率升高。结论：诱导治疗明显塑造了 cT(FH) 细胞表型KTx 后。在 KTx 前后监测 cT(FH) 细胞可能有助于检测 KTx 后容易产生 DSA 的患者。
Introduction: The cellular events that contribute to generation of donor-specific anti-HLA antibodies (DSA) post- kidney transplantation (KTx) are not well understood. Characterization of such mechanisms could allow tailoring of immunosuppression to benefit sensitized patients.Methods: We prospectively monitored circulating T follicular helper (cT(FH)) cells in KTx recipients who received T-cell depleting (thymoglobulin, n = 54) or T-cell nondepleting (basiliximab, n = 20) induction therapy from pre-KTx to 1 year post- KTx and assessed their phenotypic changes due to induction and DSA occurrence, in addition to healthy controls (n = 13), for a total of 307 blood samples.Results: Before KTx, patients displayed comparable levels of resting, central memory cT(FH) cells with similar polarization to those of healthy controls. Unlike basiliximab induction, thymoglobulin induction significantly depleted cT(FH) cells, triggered lymphopenia-induced proliferation that skewed cT(FH) cells toward increased Th1 polarization, effector memory, and elevated programmed cell death protein 1 (PD-1)(int/hi) expression, resembling activated phenotypes. Regardless of induction, patients who developed DSA post-KTx, harbored pre-KTx donor-reactive memory interleukin (IL)-21(+) cT(FH) cells and showed higher % cT(FH) and lower % of T regulatory (T-REG) cells post-KTx resulting in elevated cT(FH):T-REG ratio at DSA occurrence.Conclusion: Induction therapy distinctly shapes cT(FH) cell phenotype post-KTx. Monitoring cT(FH) cells before and after KTx may help detect those patients prone to DSA generation post-KTx.