Department of Virology, Erasmus MC, Rotterdam, The Netherlands.
Eur J Immunol. 2010 Feb;40(2):388-95. doi: 10.1002/eji.200939949.
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.
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）是淋巴亲嗜性的，感染淋巴组织中的 B 和 T 淋巴细胞的高比例。细胞免疫被认为是清除病毒的关键；然而，在初次感染期间产生的 MV 特异性 T 淋巴细胞也构成了 MV 感染的潜在目标。因此，我们旨在鉴定能够清除 MV 感染而不被感染的 T 淋巴细胞亚群。为此，我们用表达增强型 GFP 的重组 MV 株感染人 EBV 转化的 B 淋巴细胞白血病细胞系（B-LCL），并将其与未感染的 B-LCL 共培养，导致病毒迅速传播。MV 特异性 CD8(+) T 细胞克隆能够有效地抑制自体和 HLA 匹配的 B-LCL 中的 MV 传播，但不能抑制 HLA 不匹配的 B-LCL 中的 MV 传播。相比之下，CD4(+) T 细胞克隆不能控制 MV 传播，但本身成为 MV 感染的目标。此外，急性麻疹后 6-9 个月采集的 PBMC 并用自体 MV 感染的 B-LCL 刺激也能有效地抑制 MV 传播；这是由含有 CD8(+) T 淋巴细胞的部分介导的。总之，我们已经开发出一种强大的工具来研究针对麻疹的细胞免疫，并且证明 MV 传播的控制是由 MV 特异性 CD8(+)而不是 CD4(+) T 淋巴细胞介导的。
