Lilleri D, Zelini P, Fornara C, Comolli G, Gerna G
Servizio di Virologia, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy.
Am J Transplant. 2007 Aug;7(8):1997-2005. doi: 10.1111/j.1600-6143.2007.01890.x.
CD4(+) and CD8(+) T cells specific for human cytomegalovirus (HCMV) and two immunodominant HCMV antigens (pp65 and IE-1) were monitored in 20 solid organ transplant recipients undergoing primary (n = 4) or reactivated (n = 16) HCMV infection during the first year after transplantation by using as a stimulator either HCMV-infected autologous dendritic cells (DCs) or pp65- or IE-1 peptide mixtures. Turnaround times for test performance were 7 days for infected DCs and 24 h for peptides. Using infected DCs, HCMV-specific T-cell restoration occurred in all patients for CD8(+) and in 18/20 (90%) for CD4(+) T-cell subpopulations, resulting in virus clearance from blood. Using peptide mixtures, T-cell responses were less frequently detected. In detail, 14 (70%) patients showed pp65-specific CD8(+) T cells and 10 (50%) patients IE-1-specific CD8(+) T cells, whereas pp65-specific CD4(+) T cells were detected in 14 (70%) patients, and IE-1-specific CD4(+) T cells in three (15%) patients only. Protection from HCMV infection was associated with the presence of a HCMV-specific T-cell response directed against multiple viral proteins, but not against pp65 or IE-1 only. In conclusion, the use of pp65 and IE-1 peptide mixtures for rapid monitoring of HCMV-specific T-cell responses in solid organ transplant recipients underestimates the actual T-cell immune response against HCMV.
在20名实体器官移植受者中,通过使用人巨细胞病毒(HCMV)感染的自体树突状细胞(DC)或pp65或IE-1肽混合物作为刺激物,监测了针对HCMV和两种免疫显性HCMV抗原(pp65和IE-1)的CD4(+)和CD8(+) T细胞。这些受者在移植后的第一年经历了原发性(n = 4)或再激活(n = 16)HCMV感染。使用感染的DC进行检测的周转时间为7天,使用肽混合物的周转时间为24小时。使用感染的DC时,所有患者的CD8(+) T细胞亚群以及18/20(90%)的CD4(+) T细胞亚群出现了HCMV特异性T细胞恢复,导致病毒从血液中清除。使用肽混合物时,T细胞反应的检测频率较低。具体而言,14名(70%)患者显示出pp65特异性CD8(+) T细胞,10名(50%)患者显示出IE-1特异性CD8(+) T细胞,而14名(70%)患者检测到pp65特异性CD4(+) T细胞,仅3名(15%)患者检测到IE-1特异性CD4(+) T细胞。对HCMV感染的保护与针对多种病毒蛋白而非仅针对pp65或IE-1的HCMV特异性T细胞反应的存在有关。总之,在实体器官移植受者中使用pp65和IE-1肽混合物快速监测HCMV特异性T细胞反应会低估实际针对HCMV的T细胞免疫反应。