Fitzgerald-Bocarsly P, Feldman M, Curl S, Schnell J, Denny T
Department of Pathology, University of Medicine and Dentistry of New Jersey, Newark 07103.
J Immunol. 1989 Aug 15;143(4):1318-26.
Previous studies from our laboratory indicated that human NK activity against HSV-infected fibroblasts (HSV-Fs) but not K562 targets was sensitive to treatment with anti-HLA-DR plus C. In the current study, we have selected Leu-11a+ (CD-16) cells by fluorescence activated cell sorting and found that although Leu-11a enriched populations lysed K562 targets in 14-h 51Cr-release assays, they were unable to kill HSV-Fs targets unless a Leu-11a-depleted population was added back to the effectors or unless known activators of NK cells (IFN-alpha or IL-2) were added to the assays. In contrast, Leu-11a-enriched populations were able to mediate ADCC against HSV-Fs in the presence of sera from HSV-seropositive individuals without the requirement for accessory cells. We have begun preliminary characterization of the accessory cells which allow lysis of HSV-Fs by NK cells: they are HLA-DR+ cells which enrich in the light density fractions of Metrizamide density gradients. They need be present in very small numbers for lysis to take place and are not MHC restricted in that heterologous add-backs between anti-HLA-DR plus C and anti-Leu-11b plus C-treated populations are capable of target cell lysis at levels similar to those achieved with the autologous add-backs. Further, the levels of lysis in heterologous add-back experiments reflected the lytic potential of the effector rather than the accessory cell donor. Finally, although the requirement for accessory cells for NK lysis has been demonstrated for fibroblasts infected with HSV-1, CMV, and VZV, lysis of HSV-infected Raji lymphoblastoid cells is relatively accessory-cell independent, indicating that the requirement for accessory cells for lysis by NK cells is not a property of all herpesvirus-infected targets.
我们实验室之前的研究表明,人自然杀伤细胞(NK)针对单纯疱疹病毒感染的成纤维细胞(HSV - Fs)而非K562靶标的活性,对抗人白细胞抗原 - DR(anti - HLA - DR)加补体C的处理敏感。在当前研究中,我们通过荧光激活细胞分选技术筛选出Leu - 11a +(CD - 16)细胞,发现尽管Leu - 11a富集群体在14小时的51铬释放试验中能够裂解K562靶标,但除非将Leu - 11a缺失群体重新加入效应细胞中,或者向试验中添加已知的NK细胞激活剂(干扰素 - α或白细胞介素 - 2),否则它们无法杀伤HSV - Fs靶标。相比之下,在来自HSV血清阳性个体的血清存在的情况下,Leu - 11a富集群体能够介导针对HSV - Fs的抗体依赖的细胞介导的细胞毒性作用(ADCC),而无需辅助细胞。我们已经开始对允许NK细胞裂解HSV - Fs的辅助细胞进行初步表征:它们是HLA - DR +细胞,在甲泛葡胺密度梯度的低密度组分中富集。它们只需极少量存在就能发生裂解,并且不受主要组织相容性复合体(MHC)限制,因为在anti - HLA - DR加补体C和anti - Leu - 11b加补体C处理群体之间的异种回补能够以与自体回补相似的水平进行靶细胞裂解。此外,异种回补实验中的裂解水平反映的是效应细胞而非辅助细胞供体的裂解潜力。最后,尽管已经证明对于感染单纯疱疹病毒1型(HSV - 1)、巨细胞病毒(CMV)和水痘 - 带状疱疹病毒(VZV)的成纤维细胞,NK细胞裂解需要辅助细胞,但HSV感染的拉吉淋巴母细胞的裂解相对不依赖辅助细胞,这表明NK细胞裂解对辅助细胞的需求并非所有疱疹病毒感染靶标的共同特性。