CD45RA - CD25 high CD127 - CD4 + activated regulatory T cells are correlated with de novo donor-specific anti-HLA antibody formation after kidney transplantation in standard immunosuppression
CD45RA - CD25 high CD127 - CD4 + activated regulatory T cells are correlated with de novo donor-specific anti-HLA antibody formation after kidney transplantation in standard immunosuppression
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CD45RA - CD25 高 CD127 - CD4 激活的调节性 T 细胞与肾移植后标准免疫抑制中从头供体特异性抗 HLA 抗体的形成相关
DOI：
10.1016/j.intimp.2021.107661
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发表时间：
2021
影响因子：
5.6
通讯作者：
Nakamura M
中科院分区：
文献类型：
--
作者：
Tomita Y;Ishida H;Uehara S;Takiguchi S;Sato T;Nakamura M
尽管新供体特异性抗HLA抗体（dnDSA）仍然是人肾移植（KTx）的屏障，但调节性T（Treg）细胞在dnDSA形成中的作用尚不清楚。为了解决这个问题，我们评估了Treg细胞亚群在外周血单核细胞在15名健康志愿者和59 KTx受体使用流式细胞术分析。KTx组移植后CD 25 highCD 127-CD 4 +Treg细胞较健康对照组明显下调（P<0.001）。其中，11名KTx受体显示dnDSA形成，这与较低频率的CD 25 highCD 127-CD 4 +Treg细胞相关（P= .040）。此外，在总Treg细胞群中，CD 45 RA-CD 25 highCD 127-CD 4+活化Treg（aTreg）细胞在dnDSA患者中显著占主导地位（P= 0.038），而不是CD 45 RA + CD 25 highCD 127-CD 4+静息Treg细胞（P= 0.961）。相反，非供体特异性抗HLA抗体形成与CD 45 RA-aTreg细胞无关（P= .772）。多因素Logistic回归分析显示，CD 45 RA-aTreg细胞与dnDSA形成独立相关（比值比= 6.69，P = 0.040）。这些发现表明，CD 45 RA-aTreg细胞与KTx受体中的dnDSA形成密切相关，并且可能是临床诊断前抗体介导的排斥反应的重要危险因素。
Althoughde novodonor-specific anti-HLA antibodies (dnDSA) remain a barrier for human kidney transplantation (KTx), the role of regulatory T (Treg) cells in dnDSA formation remains unknown. To address this question, we evaluated Treg cell subsets in peripheral blood mononuclear cells in 15 healthy volunteers and 59 KTx recipients using flow cytometric analysis. The post-transplant CD25highCD127-CD4+Treg cells in KTx recipients were down-regulated compared with those of healthy volunteers (P< .001). Among them, 11 KTx recipients showed dnDSA formation, which was associated with lower frequencies of CD25highCD127-CD4+Treg cells (P= .040). Furthermore, of the total Treg cell population, CD45RA-CD25highCD127-CD4+activated Treg (aTreg) cells were significantly dominant in patients with dnDSA (P= .038), but not CD45RA+CD25highCD127-CD4+resting Treg cells (P= .961). In contrast, non-donor-specific anti-HLA antibody formation was not associated with CD45RA-aTreg cells (P= .772). Multivariate logistic regression analyses revealed that CD45RA-aTreg cells were independently associated with dnDSA formation (Odds ratio = 6.69,P= .040). These findings indicate that CD45RA-aTreg cells are strongly associated with dnDSA formation in KTx recipients and might be an important risk factor of antibody-mediated rejection before clinical diagnosis.