Partial recovery of disturbed V-J pairing profiles of T-cell receptor in people living with HIV receiving long-term antiretroviral therapy
Partial recovery of disturbed V-J pairing profiles of T-cell receptor in people living with HIV receiving long-term antiretroviral therapy
复制标题
接受长期抗逆转录病毒治疗的艾滋病毒感染者中 T 细胞受体 V-J 配对紊乱的部分恢复
DOI：
10.1007/s11427-020-1718-2
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发表时间：
2020-06-18
影响因子：
9.1
通讯作者：
Zeng, Hui
中科院分区：
文献类型：
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作者：
Li, Guoli;Li, Jiarui;Zeng, Hui
慢性人类免疫缺陷病毒（HIV）感染不仅引起CD4（+）T细胞的逐渐丧失，而且导致T细胞受体（TCR）曲目的干扰。在艾滋病毒（PLWH）的患者中，监测TCR库受到确定区域3（CDR3）（CDR3）和临床样本中细胞数量有限的互补性的挑战。因此，对于监测PLWH中的TCR库是必要的定量方法。我们表征了健康供体中幼稚和记忆CD4（+）T细胞的TCR V-J配对曲线，HIV感染的抗逆转录病毒疗法（ART）患者和长期（超过5年）ART经验的患者通过进行TCR测序。我们开发了一个具有18个参数的V-J指数，这些参数被细分为五个类别（表达覆盖率，最高第十个百分位数的累积百分比，多样性，个体内部相似性和个体间相似性）。在艺术患者中，18个参数中有14个显着改变。长期艺术恢复了十个参数。这四个未验证的参数与个体间的相似性有关。因此，这些发现表明，长期艺术只能部分恢复TCR V-J对并引入新影响的V-J对。此外，这些结果为TCR的V-J配对以及HIV感染中TCR曲目的干扰提供了新的见解。
Chronic human immunodeficiency virus (HIV) infection not only causes a gradual loss of CD4(+)T cells but also leads to a disturbance of the T cell receptor (TCR) repertoire. In people living with HIV (PLWH), monitoring TCR repertoire is challenged by the inconsistency of complementarity determining region 3 (CDR3) and limited cell numbers in clinical samples. Thus, a quantitative method is necessary for monitoring the TCR repertoire in PLWH. We characterized the TCR V-J pairing profile of naive and memory CD4(+)T cells in healthy donors, HIV-infected antiretroviral therapy (ART)-naive patients and long-term (over 5 years) ART-experienced patients by performing TCR sequencing. We developed a V-J index with 18 parameters which were subdivided into five categories (expression coverage, cumulative percentage of the top tenth percentile, diversity, intra-individual similarity and inter-individual similarity). In ART-naive patients, 14 of the 18 parameters were significantly altered. Long-term ART recovered ten parameters. The four unrecovered parameters were related to inter-individual similarity. Therefore, these findings indicate that long-term ART could only partially recover TCR V-J pairs and introduce newly impacted V-J pairs. Moreover, these results provide new insights into the V-J pairing of the TCR and into the disturbance of TCR repertoire in HIV infection.