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巨细胞病毒(CMV)pp65和即刻早期-1特异性CD8(+) T细胞的功能模式,这些模式与异基因干细胞移植后预防和控制CMV血症相关。

Functional patterns of cytomegalovirus (CMV) pp65 and immediate early-1-specific CD8(+) T cells that are associated with protection from and control of CMV DNAemia after allogeneic stem cell transplantation.

作者信息

Giménez E, Muñoz-Cobo B, Solano C, Amat P, de la Cámara R, Nieto J, López J, Remigia M J, Garcia-Noblejas A, Navarro D

机构信息

Microbiology Service, Hospital Clínico Universitario, Fundación INCLIVA, Valencia, Spain.

Hematology and Medical Oncology Service, Hospital Clínico Universitario, Fundación INCLIVA, Valencia, Spain.

出版信息

Transpl Infect Dis. 2015 Jun;17(3):361-70. doi: 10.1111/tid.12391. Epub 2015 Jun 1.

Abstract

BACKGROUND

The functional profile of cytomegalovirus (CMV)-specific CD8(+) T cells that associate with protection from and control of CMV DNAemia in allogeneic stem cell transplant (allo-SCT) recipients remains incompletely characterized.

METHODS

We enumerated pp65 and immediate early (IE)-1-specific CD8(+) T cells expressing interferon-gamma, tumor necrosis factor-alpha, and CD107a, by flow cytometry in 94 patients at days +30 and +60 after allo-SCT.

RESULTS

Fifty of 94 patients had CMV DNAemia within the first 100 days after transplant. CMV-specific CD8(+) T-cell responses (of any functional type) were more likely to be detected in patients who did not display CMV DNAemia than in those who did (P = 0.04). Qualitatively, no major differences in the functional signature of CMV-specific CD8(+) T cells were noted between patients who had or did not have CMV DNAemia. Patients displaying levels of polyfunctional CD8(+) T cells at day +30 >0.30 cell/μL had a lower risk of CMV DNAemia (positive predictive value 76%, and negative predictive value 43%).

CONCLUSION

The presence of polyfunctional CD8(+) T cells (either expressing CD107a or not) was associated with lower levels of CMV replication, and higher frequency of self-resolved episodes. The data reported further clarify the role of polyfunctional CD8(+) T cells in control of CMV DNAemia in allo-SCT recipients.

摘要

背景

在异基因干细胞移植(allo-SCT)受者中,与预防和控制巨细胞病毒(CMV)血症相关的CMV特异性CD8(+) T细胞的功能特征仍未完全明确。

方法

我们通过流式细胞术对94例allo-SCT患者在移植后第30天和第60天表达干扰素-γ、肿瘤坏死因子-α和CD107a的pp65和即刻早期(IE)-1特异性CD8(+) T细胞进行了计数。

结果

94例患者中有50例在移植后的前100天内出现CMV血症。未出现CMV血症的患者比出现CMV血症的患者更有可能检测到CMV特异性CD8(+) T细胞反应(任何功能类型)(P = 0.04)。定性分析显示,出现或未出现CMV血症的患者之间,CMV特异性CD8(+) T细胞的功能特征没有重大差异。在第30天多能CD8(+) T细胞水平>0.30细胞/μL的患者发生CMV血症的风险较低(阳性预测值为76%,阴性预测值为43%)。

结论

多能CD8(+) T细胞(无论是否表达CD107a)的存在与较低水平的CMV复制以及较高的自我缓解发生率相关。报告的数据进一步阐明了多能CD8(+) T细胞在allo-SCT受者控制CMV血症中的作用。

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