Paya C V, Kenmotsu N, Schoon R A, Leibson P J
Department of Immunology, Mayo Clinic and Foundation, Rochester, MN 55905.
J Immunol. 1988 Sep 15;141(6):1989-95.
NK cells mediate their cytotoxicity against tumor cells through abroad array of cytotoxic and cytostatic proteins. We investigated whether specific proteins could also be identified that contributed to NK cell-mediated antiviral immunity. Human CD16+/CD3- NK cells were obtained by using FACS and subsequently cloned by using limiting dilution. These NK cell lines, which were cytotoxic against NK-sensitive tumor targets and virally infected cells, also generated supernatants that selectively killed vesicular stomatitis virus-infected cells while sparing noninfected cells. This soluble antiviral activity was completely neutralized by antibodies specific for TNF and lymphotoxin. Purified human rTNF also duplicated this specific cytotoxicity against vesicular stomatitis virus-infected cells, as well as against CMV-, Theiler's murine encephalomyelitis virus-, and HSV-infected cells. The degree of cytotoxicity varied for the different viruses and depended on the cell type infected. These results suggest that NK cells can mediate selective and direct cytotoxicity against virally infected cells by the secretion of TNF and lymphotoxin.
自然杀伤细胞通过一系列广泛的细胞毒性和细胞生长抑制蛋白介导其对肿瘤细胞的细胞毒性作用。我们研究了是否也能鉴定出有助于自然杀伤细胞介导的抗病毒免疫的特定蛋白质。通过使用荧光激活细胞分选术（FACS）获得人CD16 + / CD3 - 自然杀伤细胞，随后通过有限稀释法进行克隆。这些对自然杀伤细胞敏感的肿瘤靶标和病毒感染细胞具有细胞毒性的自然杀伤细胞系，还产生了能选择性杀死水疱性口炎病毒感染细胞而不损伤未感染细胞的上清液。这种可溶性抗病毒活性被针对肿瘤坏死因子（TNF）和淋巴毒素的特异性抗体完全中和。纯化的人重组肿瘤坏死因子（rTNF）也重现了这种对水疱性口炎病毒感染细胞以及对巨细胞病毒（CMV）、泰勒氏小鼠脑脊髓炎病毒（Theiler's murine encephalomyelitis virus）和单纯疱疹病毒（HSV）感染细胞的特异性细胞毒性。不同病毒的细胞毒性程度各不相同，且取决于所感染的细胞类型。这些结果表明，自然杀伤细胞可通过分泌肿瘤坏死因子和淋巴毒素介导对病毒感染细胞的选择性和直接细胞毒性作用。
