Litjens Nicolle H R, Huang Ling, Dedeoglu Burç, Meijers Ruud W J, Kwekkeboom Jaap, Betjes Michiel G H
Department of Internal Medicine, Nephrology and Transplantation, Erasmus MC, University Medical Center Rotterdam, Rotterdam, Netherlands.
Department of Gastroenterology and Hepatology, Erasmus MC, University Medical Center Rotterdam, Rotterdam, Netherlands.
Front Immunol. 2017 Sep 12;8:1137. doi: 10.3389/fimmu.2017.01137. eCollection 2017.
The absence of anti-cytomegalovirus (CMV) immunoglobulin G (IgG) is used to classify pretransplant patients as naïve for CMV infection (CMV patients). This study assessed whether pretransplant CMV-specific T-cell immunity exists in CMV patients and whether it protects against CMV infection after kidney transplantation. The results show that CMV-specific CD137IFNγCD4 and CD137IFNγCD8 memory T cells were present in 46 and 39% of CMV patients ( = 28) although at much lower frequencies compared to CMV patients (median 0.01 versus 0.58% for CD4 and 0.05 versus 0.64% for CD8 T cells) with a less differentiated CD28-expressing phenotype. In line with these data, CMV-specific proliferative CD4 and CD8 T cells were observed in CMV patients, which significantly correlated with the frequency of CMV-specific T cells. CMV-specific IgG antibody-secreting cells (ASC) could be detected at low frequency in 36% of CMV patients (1 versus 45 ASC/10 cells in CMV patients). CMV patients with pretransplant CMV-specific CD137IFNγCD4 T cells had a lower risk to develop CMV viremia after transplantation with a CMV donor kidney (relative risk: 0.43, = 0.03). In conclusion, a solitary CMV-specific T-cell response without detectable anti-CMV antibodies is frequent and clinically relevant as it is associated with protection to CMV infection following transplantation with a kidney from a CMV donor.
抗巨细胞病毒(CMV)免疫球蛋白G(IgG)的缺失用于将移植前患者分类为未感染CMV(CMV初免患者)。本研究评估了CMV初免患者移植前是否存在CMV特异性T细胞免疫,以及它是否能预防肾移植后CMV感染。结果显示,46%和39%的CMV初免患者(n = 28)存在CMV特异性CD137 IFNγ CD4和CD137 IFNγ CD8记忆T细胞,尽管与CMV感染患者相比频率要低得多(CD4 T细胞中位数为0.01%对0.58%,CD8 T细胞为0.05%对0.64%),且具有表达CD28的分化程度较低的表型。与这些数据一致,在CMV初免患者中观察到CMV特异性增殖性CD4和CD8 T细胞,其与CMV特异性T细胞频率显著相关。在36%的CMV初免患者中可低频率检测到CMV特异性IgG抗体分泌细胞(ASC)(CMV感染患者中为1对45个ASC/10⁶细胞)。移植CMV供体肾脏后,移植前具有CMV特异性CD137 IFNγ CD4 T细胞的CMV初免患者发生CMV病毒血症的风险较低(相对风险:0.43,P = 0.03)。总之,在无可检测到的抗CMV抗体情况下,单独的CMV特异性T细胞反应很常见且具有临床相关性,因为它与移植CMV供体肾脏后的CMV感染保护相关。