Impaired cytotoxic T lymphocyte response to Epstein‐Barr virus‐infected NK cells in patients with severe chronic active EBV infection
Impaired cytotoxic T lymphocyte response to Epstein‐Barr virus‐infected NK cells in patients with severe chronic active EBV infection
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DOI：
10.1002/jmv.1029
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发表时间：
2001-06
影响因子：
12.7
通讯作者：
I. Tsuge;T. Morishima;H. Kimura;K. Kuzushima;H. Matsuoka
中科院分区：
文献类型：
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作者：
I. Tsuge;T. Morishima;H. Kimura;K. Kuzushima;H. Matsuoka
严重慢性活动性 Epstein-Barr 病毒 (EBV) 感染与 EBV 感染的 T 或 NK 细胞克隆扩增之间存在关系的临床证据已经积累。为了阐明严重慢性活动性 EBV 感染患者中 EBV 感染细胞增殖的发病机制，我们检查了两名患者对 B 类淋巴母细胞系 (B-LCL) 和 EBV 感染 NK 细胞的细胞毒性 T 淋巴细胞 (CTL) 反应，并与 HLA 相同的健康兄弟姐妹进行比较。出乎意料的是，尽管从未出现过不受控制的 EBV 相关 B 细胞增殖，但与自体 B-LCL 混合培养诱导的患者 CTL 活性显着降低。相反，有限稀释分析表明，患者的 B-LCL 特异性 CTL 前体 (CTLp) 频率与其健康姐妹的频率相当。通过对 B-LCL 刺激后产生 IFN-γ 的 T 细胞进行流式细胞术分析，证实了正常水平的 B-LCL 特异性 T 细胞反应的存在。尽管患者表达潜伏膜蛋白（LMP）1，但受感染的 NK 细胞特异性 CTLp 频率仍处于不可检测的水平，这表明有逃避免疫监视的机制。在患者的 HLA 相同的健康姐妹中，检测到了受感染的 NK 细胞特异性 CTL，并且可以建立受感染的 NK 细胞特异性 CTL 克隆。根据这些发现，针对严重慢性活动性 EBV 感染提供了两种可供考虑的治疗方案：体外培养的 CTL 的过继转移和 HLA 相同供体的骨髓移植。 J. Med。病毒。 64:141–148, 2001。© 2001 Wiley-Liss, Inc.
Clinical evidence of a relationship between severe chronic active Epstein‐Barr virus (EBV) infection and clonal expansion of EBV‐infected T or NK cells has been accumulated. In order to clarify pathogenesis of EBV‐infected cell proliferation in patients with severe chronic active EBV infection, cytotoxic T lymphocyte (CTL) responses of two patients against B‐lymphoblastoid cell lines (B‐LCL) and EBV‐infected NK cells were examined in comparison with those of HLA‐identical healthy siblings. Unexpectedly, patients' CTL activities induced by mixed culture with autologous B‐LCLs were markedly reduced, although uncontrolled EBV‐related B‐cell proliferations have never been experienced. In contrast, limiting dilution analysis demonstrated that B‐LCL‐specific CTL precursor (CTLp) frequencies of patients were comparable to those of their healthy sisters. The existence of normal levels of B‐LCL‐specific T cell responses was confirmed by flow‐cytometric analysis of IFN‐γ‐producing T cells after stimulation with B‐LCLs. Infected NK‐cell‐specific CTLp frequencies of the patients were at undetectable levels despite their expression of latent membrane protein (LMP) 1, suggesting mechanisms to escape immunologic surveillance. In the patients' HLA‐identical healthy sisters, infected NK‐cell‐specific CTLps were detected, and infected NK‐cell‐specific CTL clones could be established. From these findings, two treatment options for severe chronic active EBV infection are offered for consideration: adoptive transfer of in vitro‐cultured CTL, and bone marrow transplantation from HLA‐identical donors. J. Med. Virol. 64:141–148, 2001. © 2001 Wiley‐Liss, Inc.