Multi-Organ Transplant Program, Department of Medicine, University Health Network, Toronto, ON, Canada.
Transplantation. 2020 Nov;104(11):2373-2382. doi: 10.1097/TP.0000000000003130.
Epstein-Barr virus (EBV) DNAemia is a major risk factor for posttransplant lymphoproliferative disorder; however, immune correlates of EBV DNAemia in the transplant setting are limited.
Peripheral blood mononuclear cells were collected from 30 transplant recipients with self-limiting EBV DNAemia (SLD; n = 11) or chronic EBV DNAemia (CD; n = 19) at enrollment and 4-8 weeks later. Mass cytometry was used to characterize innate and T-cell immune correlates of EBV DNAemia. Furthermore, flow cytometry was used to measure the frequency of EBV-specific T-cell responses between groups following stimulation with an EBV-infected cell lysate.
Unsupervised analysis of the innate compartment (CD3CD19 cells) identified 5 CD11c clusters at higher abundance in the SLD group (false discovery rate ≤ 1%). These clusters expressed CD11b, CD45RO, CD14, CD123, CD127, and CD38, among others. Unsupervised profiling of the T-cell compartment (CD3CD19) revealed 2 CD4 T-cell clusters at higher frequency among those with SLD (false discovery rate ≤ 1%), which expressed CD45RA, CCR7, CD27, CD28, and CD40L-suggestive of a naive T cell (TN). Manual biaxial gating confirmed increased frequencies of conventional dendritic cells (3.1% versus 2.1%; P = 0.023) and CD4 TN (4.4% versus 1.9%; P = 0.018) among those with SLD. Last, frequencies of interferon-γ-producing EBV-specific CD4 T cells were significantly lower in the CD group relative to those with SLD (4243 versus 250 cells/10 cells; P = 0.015).
CD is associated with a reduction of CD11c cells, CD4 TN, and interferon-γ-producing EBV-specific CD4 T cells, suggesting an interplay between innate and adaptive immune compartments may be important for regulating EBV DNAemia.
Epstein-Barr 病毒 (EBV) DNA 血症是移植后淋巴组织增生性疾病的主要危险因素；然而，移植环境中 EBV DNA 血症的免疫相关性有限。
在入组时和 4-8 周后，采集 30 例有自限性 EBV DNA 血症（SLD；n=11）或慢性 EBV DNA 血症（CD；n=19）的移植受者的外周血单个核细胞。使用质谱流式细胞术来描述 EBV DNA 血症的固有和 T 细胞免疫相关性。此外，使用流式细胞术测量在 EBV 感染细胞裂解物刺激后各组 EBV 特异性 T 细胞反应的频率。
对固有部分（CD3CD19 细胞）进行无监督分析，发现 SLD 组中有 5 个 CD11c 簇的丰度更高（错误发现率≤1%）。这些簇表达 CD11b、CD45RO、CD14、CD123、CD127 等。对 T 细胞部分（CD3CD19）进行无监督分析，发现 SLD 组中有 2 个 CD4 T 细胞簇的频率更高（错误发现率≤1%），这些簇表达 CD45RA、CCR7、CD27、CD28 和 CD40L，提示为幼稚 T 细胞（TN）。手动双轴门控确认 SLD 组中常规树突状细胞（3.1%比 2.1%；P=0.023）和 CD4 TN（4.4%比 1.9%；P=0.018）的频率增加。最后，CD 组中 IFN-γ 产生的 EBV 特异性 CD4 T 细胞的频率明显低于 SLD 组（4243 比 250 个细胞/10 个细胞；P=0.015）。
CD 与 CD11c 细胞、CD4 TN 和 IFN-γ 产生的 EBV 特异性 CD4 T 细胞的减少有关，这表明固有和适应性免疫细胞之间的相互作用可能对调节 EBV DNA 血症很重要。
