人类疱疹病毒6型：致瘤性与肿瘤浸润淋巴细胞

Human herpesvirus-6: tumorigenicity and tumor infiltrating lymphocytes.

作者信息

Razzaque A, Puri R K

机构信息

Division of Virology, FDA, Bethesda, MD 20892.

出版信息

Cancer Lett. 1992 Jan 10;61(2):111-8. doi: 10.1016/0304-3835(92)90168-u.

DOI:10.1016/0304-3835(92)90168-u

PMID:1309683

Abstract

We previously reported that human herpes-virus-6 (HHV-6) genome (strain GS) and a cloned subfragment (pZVH14) transfected NIH 3T3 cells, induced foci of transformation with a frequency significantly above the background level. The transformed cells produced tumors in nude mice and immunocompetent (Swiss) mice. In the current study, nude mice tumors were passed into Swiss mice and more aggressive tumors (G-2TS and 14-2TS derived from HHV-6 genome and pZVH14 DNA, respectively) were produced. 14-2TS tumors caused lung metastasis upon intravenous injection. In the case of subcutaneously growing aggressive tumors, tumor infiltrating lymphocytes (TIL) were isolated and characterized as T cells but lacked tumor specific killing as monitored by 51Cr-release assays. TIL lost activity at day 52 in a 4 h assay (but not in a 19 h assay) against the autologous tumor, but not a Maloney virus induced tumor (Yac-1). These studies indicate that an established nontumorigenic fibroblast cell line, when transfected with pZVH14 DNA of HHV-6, acquires both tumorigenic and metastatic potential and tumor bearing hosts mount immune response against such tumors.

摘要

我们先前报道，人疱疹病毒6型（HHV-6）基因组（GS株）和一个克隆的亚片段（pZVH14）转染NIH 3T3细胞后，诱导转化灶的频率显著高于背景水平。转化细胞在裸鼠和免疫健全（瑞士）小鼠体内产生肿瘤。在当前研究中，将裸鼠肿瘤接种到瑞士小鼠体内，产生了更具侵袭性的肿瘤（分别源自HHV-6基因组和pZVH14 DNA的G-2TS和14-2TS）。14-2TS肿瘤静脉注射后会引起肺转移。对于皮下生长的侵袭性肿瘤，分离出肿瘤浸润淋巴细胞（TIL），鉴定为T细胞，但通过51Cr释放试验监测发现其缺乏肿瘤特异性杀伤能力。在4小时试验中（但在19小时试验中未出现），TIL在第52天对自体肿瘤失去活性，但对莫洛尼病毒诱导的肿瘤（Yac-1）没有失去活性。这些研究表明，一种已建立的非致瘤性成纤维细胞系，当用HHV-6的pZVH14 DNA转染后，获得了致瘤和转移潜能，并且荷瘤宿主会针对此类肿瘤产生免疫反应。