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人类疱疹病毒 6T 细胞反应的首次分析:干细胞移植受者 HHV6 再激活后的特异性增强。

First analysis of human herpesvirus 6T-cell responses: specific boosting after HHV6 reactivation in stem cell transplantation recipients.

机构信息

Dept. of Immunology, Hematology and SCT, University Medical Center Utrecht, The Netherlands.

出版信息

Clin Immunol. 2012 Sep;144(3):179-89. doi: 10.1016/j.clim.2012.06.006. Epub 2012 Jun 30.

DOI:10.1016/j.clim.2012.06.006
PMID:22820131
Abstract

Early human herpesvirus 6 (HHV6) reactivation after hematopoietic stem cell transplantation (HSCT) is associated with poor survival. We characterized HHV6 immuneresponses in HSCT patients during lymphopenia. Prospectively, HHV6 DNA-load was measured weekly by realtime-PCR. Numbers of IFNγ-producing HHV6-T-cells were retrospectively determined by enzyme-linked immunospot assay 2 months after HSCT. HHV6-specific T-cell proliferative capacity was analyzed with a newly developed assay using antigen-presenting autologous HHV6-infected PBMC. Fifty-six patients were included (median age 4.6 years; range 0.2-21.2 years). HHV6-reactivation occurred in 29/56 (52%) patients with a median time of 14 (range 1-41) days after HSCT. The median number of IFN-γ producing HHV6-specific T-cells at 2 months and the HHV6-specific CD8+ T-cell proliferative capacity at 6 months after HSCT was increased after HHV6-reactivation compared to non-reactivating patients (P=0.006 and p=0.019). In conclusion, HHV6-specific immuneresponses can be initiated during lymphopenia early after HSCT, which implicates a potential window for development of HHV6-specific (immuno)therapy.

摘要

造血干细胞移植(HSCT)后早期人类疱疹病毒 6(HHV6)再激活与生存不良有关。我们在淋巴细胞减少症期间对 HSCT 患者的 HHV6 免疫反应进行了特征描述。前瞻性地,通过实时 PCR 每周测量 HHV6 DNA 载量。在 HSCT 后 2 个月,通过酶联免疫斑点分析回顾性地确定产生 IFNγ的 HHV6-T 细胞的数量。使用新开发的使用抗原呈递自体 HHV6 感染的 PBMC 的测定法分析了 HHV6 特异性 T 细胞的增殖能力。共纳入 56 例患者(中位年龄 4.6 岁;范围 0.2-21.2 岁)。HHV6 再激活发生在 56 例患者中的 29 例(52%),HSCT 后中位数时间为 14 天(范围 1-41 天)。与未再激活的患者相比,HSCT 后 2 个月的 IFN-γ产生 HHV6 特异性 T 细胞的中位数数量和 HHV6 特异性 CD8+ T 细胞增殖能力在 HHV6 再激活后增加(P=0.006 和 p=0.019)。总之,HHV6 特异性免疫反应可以在 HSCT 后早期的淋巴细胞减少症期间启动,这暗示了开发 HHV6 特异性(免疫)治疗的潜在窗口。

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