Ozdemir Evren, St John Lisa S, Gillespie Geraldine, Rowland-Jones Sarah, Champlin Richard E, Molldrem Jeffrey J, Komanduri Krishna V
Transplant Immunology Section, Department of Blood and Marrow Transplantation, University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
Blood. 2002 Nov 15;100(10):3690-7. doi: 10.1182/blood-2002-05-1387. Epub 2002 Jul 5.
Cytomegalovirus (CMV) infection causes significant morbidity and mortality in the setting of immunodeficiency, including the immune reconstitution phase following allogeneic stem cell transplantation (SCT). We assessed CMV-specific CD4(+) and CD8(+) T-cell responses in 87 HLA-A0201-positive (A2+) and/or B0702-positive (B7+) allogeneic stem cell transplant recipients using HLA-peptide tetramer staining and cytokine flow cytometry (CFC) to examine the association of CMV-specific immune reconstitution and CMV antigenemia following SCT. Strong CMV-specific T-cell responses recovered in most subjects (77 of 87, 88%) after SCT. Frequencies of CMV-specific CD8(+) T cells were significantly higher in those subjects who experienced early antigenemia relative to those who did not (2.2% vs 0.33%, P =.0002), as were frequencies of CMV-specific CD4(+) T cells (1.71% vs 0.75%, P =.002). Frequencies of CMV-specific CD8(+) T cells were also higher in subjects experiencing late antigenemia (2.4% vs 0.57%). When we combined tetramer staining and an assessment of cytokine production in a single assay, we found that individuals who experienced CMV antigenemia had lower tumor necrosis factor-alpha (TNF-alpha)-producing fractions of tetramer-staining CMV-specific CD8(+) T cells than subjects who did not (25% vs 65%, P =.015). Furthermore, individuals at high risk for CMV reactivation, including patients with acute graft-versus-host disease and those receiving steroids, had low fractions of cytokine-producing CMV-specific CD8(+) T cells (25% and 27%, respectively). These data suggest that the inability to control CMV reactivation following allogeneic SCT is due to the impaired function of antigen-specific CD8(+) T cells rather than an inability to recover sufficient numbers of CMV-specific T cells.
巨细胞病毒（CMV）感染在免疫缺陷情况下会导致显著的发病率和死亡率，包括异基因干细胞移植（SCT）后的免疫重建阶段。我们使用HLA肽四聚体染色和细胞因子流式细胞术（CFC）评估了87名HLA - A0201阳性（A2 +）和/或B0702阳性（B7 +）的异基因干细胞移植受者中CMV特异性CD4(+)和CD8(+) T细胞反应，以研究SCT后CMV特异性免疫重建与CMV抗原血症之间的关联。大多数受试者（87名中的77名，88%）在SCT后恢复了强烈的CMV特异性T细胞反应。与未经历早期抗原血症的受试者相比，经历早期抗原血症的受试者中CMV特异性CD8(+) T细胞频率显著更高（2.2%对0.33%，P = 0.0002），CMV特异性CD4(+) T细胞频率也是如此（1.71%对0.75%，P = 0.002）。经历晚期抗原血症的受试者中CMV特异性CD8(+) T细胞频率也更高（2.4%对0.57%）。当我们在单一检测中结合四聚体染色和细胞因子产生评估时，我们发现经历CMV抗原血症的个体中，产生肿瘤坏死因子 - α（TNF - α）的四聚体染色CMV特异性CD8(+) T细胞比例低于未经历抗原血症的受试者（25%对65%，P = 0.015）。此外，CMV再激活高危个体，包括患有急性移植物抗宿主病的患者和接受类固醇治疗的患者，产生细胞因子的CMV特异性CD8(+) T细胞比例较低（分别为25%和27%）。这些数据表明，异基因SCT后无法控制CMV再激活是由于抗原特异性CD8(+) T细胞功能受损，而非无法恢复足够数量的CMV特异性T细胞。
