Malnati M S, Lusso P, Ciccone E, Moretta A, Moretta L, Long E O
Laboratory of Immunogenetics, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, Maryland 20852.
J Exp Med. 1993 Sep 1;178(3):961-9. doi: 10.1084/jem.178.3.961.
Natural killer (NK) cells provide a first line of defense against viral infections. The mechanisms by which NK cells recognize and eliminate infected cells are still largely unknown. To test whether target cell elements contribute to NK cell recognition of virus-infected cells, human NK cells were cloned from two unrelated donors and assayed for their ability to kill normal autologous or allogeneic cells before and after infection by human herpesvirus 6 (HHV-6), a T-lymphotropic herpesvirus. Of 132 NK clones isolated from donor 1, all displayed strong cytolytic activity against the NK-sensitive cell line K562, none killed uninfected autologous T cells, and 65 (49%) killed autologous T cells infected with HHV-6. A panel of representative NK clones from donors 1 and 2 was tested on targets obtained from four donors. A wide heterogeneity was observed in the specificity of lysis of infected target cells among the NK clones. Some clones killed none, some killed only one, and others killed more than one of the different HHV-6-infected target cells. Killing of infected targets was not due to complete absence of class I molecules because class I surface levels were only partially affected by HHV-6 infection. Thus, target cell recognition is not controlled by the effector NK cell alone, but also by polymorphic elements on the target cell that restrict NK cell recognition. Furthermore, NK clones from different donors display a variable range of specificities in their recognition of infected target cells.
自然杀伤（NK）细胞为抵抗病毒感染提供了第一道防线。NK细胞识别并清除受感染细胞的机制在很大程度上仍然未知。为了测试靶细胞成分是否有助于NK细胞识别病毒感染细胞，从两名无关供体中克隆了人NK细胞，并检测它们在感染人嗜T淋巴细胞疱疹病毒6型（HHV - 6）前后杀死正常自体或同种异体细胞的能力。从供体1分离出的132个NK克隆中，所有克隆都对NK敏感细胞系K562表现出强烈的细胞溶解活性，没有一个克隆能杀死未感染的自体T细胞，65个（49%）克隆能杀死感染HHV - 6的自体T细胞。对来自供体1和供体2的一组代表性NK克隆在从四名供体获得的靶细胞上进行了测试。在NK克隆中观察到感染靶细胞裂解特异性存在广泛的异质性。一些克隆不杀死任何靶细胞，一些克隆只杀死一种，而其他克隆能杀死不止一种不同的HHV - 6感染靶细胞。对感染靶细胞的杀伤并非由于完全缺乏I类分子，因为I类分子的表面水平仅受到HHV - 6感染的部分影响。因此，靶细胞识别不仅由效应NK细胞控制，还由限制NK细胞识别的靶细胞上的多态性成分控制。此外，来自不同供体的NK克隆在识别感染靶细胞时表现出不同范围的特异性。
