Shiraz Transplant Research Center, Shiraz University of Medical Sciences, Shiraz, Iran.
Shiraz Transplant Research Center, Shiraz University of Medical Sciences, Shiraz, Iran.
Transpl Immunol. 2021 Dec;69:101460. doi: 10.1016/j.trim.2021.101460. Epub 2021 Sep 4.
Cytomegalovirus (CMV) infection contributes to morbidity and mortality among kidney transplant recipients. Natural killer (NK) cells can battle against CMV in kidney transplant recipients (KTRs). This study aimed to analyze the association between CMV reactivation and the proportion of NK cell subsets and their activity. In a cross-sectional study, ten CMV reactivated KTRs, and ten non- CMV reactivated ones were recruited. Ten matched healthy controls were also included in this cohort. The presence of anti-CMV-IgG Ab in both KTR subgroups from seronegative donors and healthy controls was determined. The frequency of distinct subsets of memory-like NK cells was analyzed through NKG2C, NKG2A, and CD57 using flow cytometry. The activity of NK cells was evaluated after stimulation via coculture with K562 cell line and then assessment of the frequency of CD107a and granzyme B. The mRNA levels of transcription factors, including T-bet, EAT, and inflammatory proteins, including IFN-γ and perforin contributing to NK cell activation, were also evaluated. Results showed a significantly lower frequency of NKG2C + NKG2A-CD57+ NK cell population in CMV-reactivated KTRs compared to non-reactivated ones (P-value:0.003). NKG2C+ NK cells expressing CD107a/LAMP-1 significantly was increased in CMV-reactivated KTRs compared to non-reactivated ones (P-value: 0.0002). The mRNA level of IFN-γ had a significant increase in the CMV-reactivated KTRs vs. nonreactive ones (P-value: 0.004). Finally, evaluation of the NK cells' cytotoxicity and activity through assessment of CD107a/LAMP-1 expression and IFN-γ secretion may be helpful for the identification of the risk of CMV reactivation in KTRs.
巨细胞病毒 (CMV) 感染是导致肾移植受者发病率和死亡率的原因之一。自然杀伤 (NK) 细胞可以在肾移植受者 (KTR) 中对抗 CMV。本研究旨在分析 CMV 再激活与 NK 细胞亚群及其活性的比例之间的关系。在一项横断面研究中，招募了 10 名 CMV 再激活的 KTR 和 10 名非 CMV 再激活的 KTR。该队列还纳入了 10 名匹配的健康对照者。通过酶联免疫吸附试验 (ELISA) 检测来自血清阴性供者和健康对照者的 KTR 亚组的抗 CMV-IgG Ab 的存在情况。通过流式细胞术分析 NKG2C、NKG2A 和 CD57 鉴定记忆样 NK 细胞的不同亚群的频率。通过与 K562 细胞系共培养后刺激 NK 细胞，并评估 CD107a 和 granzyme B 的频率，评估 NK 细胞的活性。还评估了转录因子 T-bet、EAT 和炎症蛋白 IFN-γ 和穿孔素的 mRNA 水平，这些蛋白有助于 NK 细胞的激活。结果显示，与非再激活者相比，CMV 再激活的 KTR 中 NKG2C+NKG2A-CD57+ NK 细胞群的频率显著降低（P 值：0.003）。与非再激活者相比，CMV 再激活的 KTR 中表达 CD107a/LAMP-1 的 NKG2C+ NK 细胞显著增加（P 值：0.0002）。与非再激活者相比，CMV 再激活的 KTR 中 IFN-γ 的 mRNA 水平显著增加（P 值：0.004）。最后，通过评估 CD107a/LAMP-1 表达和 IFN-γ 分泌来评估 NK 细胞的细胞毒性和活性，可能有助于识别 KTR 中 CMV 再激活的风险。
