Specific CD8+ T-lymphocytes control dissemination of measles virus
Specific CD8+ T-lymphocytes control dissemination of measles virus
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DOI：
10.1002/eji.200939949
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发表时间：
2010-02-01
影响因子：
5.4
通讯作者：
de Swart, Rik L.
中科院分区：
文献类型：
--
作者：
de Vries, Rory D.;Yuksel, Selma;de Swart, Rik L.
麻疹仍然是发展中国家儿童死亡的一个重要原因。麻疹病毒（MV）是嗜淋巴的，并且感染淋巴组织中高百分比的B-和T-淋巴细胞。细胞免疫被认为是病毒清除的关键;然而，MV特异性T淋巴细胞在原发性感染过程中产生的也构成了MV感染的潜在目标。因此，我们的目的是确定T淋巴细胞亚群，可以清除MV感染，而不会被感染。为此，我们用表达增强的GFP的重组MV株感染人EBV转化的B淋巴母细胞细胞系（B-LCL），并将其与未感染的B-LCL共培养，导致病毒快速扩散。MV特异性CD 8（+）T细胞克隆有效抑制了自体和HLA匹配的MV传播，但在HLA不匹配的B-LCL中无效。相反，CD 4（+）T细胞克隆不能控制MV传播，但本身成为MV感染的靶点。此外，在急性麻疹后6-9个月收集的PBMC用自体MV感染的B-LCL刺激也有效地抑制了MV传播;这是由含有CD 8（+）T淋巴细胞的部分介导的。总之，我们已经开发了一种研究麻疹细胞免疫的有力工具，并证明MV传播的控制是由病毒特异性CD 8（+）而不是CD 4（+）T淋巴细胞介导的。
Measles continues to be an important cause of childhood mortality in developing countries. Measles virus (MV) is lymphotropic and infects high percentages of B- and T-lymphocytes in lymphoid tissues. Cellular immunity is considered crucial for viral clearance; however, MV-specific T-lymphocytes generated during primary infection also constitute a potential target for MV infection. We therefore aimed to identify T-lymphocyte subsets that can clear MV infection without becoming infected. To this end, we infected human EBV transformed B-lymphoblastic cell lines (B-LCL) with a recombinant MV strain expressing enhanced GFP, and co-cultured these with non-infected B-LCL resulting in rapid viral spread. MV-specific CD8(+) T-cell clones efficiently suppressed MV dissemination in autologous and HLA-matched, but not in HLA-mismatched B-LCL. In contrast, CD4(+) T-cell clones could not control MV dissemination but became a target for MV infection themselves. Furthermore, PBMC collected 6-9 months after acute measles and stimulated with autologous MV-infected B-LCL also efficiently suppressed Mv dissemination; this was mediated by the fraction containing CD8(+) T-lymphocytes. in conclusion, we have developed a powerful tool to study cellular immunity against measles, and demonstrate that control of MV dissemination is mediated by virus-specific CD8(+) rather than by CD4(+) T-lymphocytes.