Ohshima K, Suzumiya J, Shimazaki K, Kato A, Tanaka T, Kanda M, Kikuchi M
Department of Pathology, School of Medicine, Fukuoka University, Japan.
Histopathology. 1997 Nov;31(5):444-50. doi: 10.1046/j.1365-2559.1997.2880887.x.
Two molecular mechanisms of T/natural killer (NK) cell-mediated cytotoxicity, one perforin based and the other Fas based, have been demonstrated, and both systems induce cytotoxicity in the target cells. The Fas-based mechanism involves the transducing molecule Fas and its ligand (FasL). In addition, perforin and/or FasL are also expressed in the cytotoxic T/NK cells. This study was thus designed to investigate the Fas and perforin pathways of the cytotoxic T/NK lymphoma cells in the nasal cavity.
Eight patients with nasal lymphoma were analysed using immunohistochemical staining methods. Two cases were CD3+ CD56+ (T/NK cell) type, and six were CD3- CD56+ (NK cell) type. All cases showed Epstein-Barr virus genomes by in-situ hybridization. In addition, all cases showed the expression of TIA-1 (GMP-17), which is a marker of cytotoxic T and NK cells. FasL was expressed in the majority of the lymphoma cells and some histiocytes, while Fas was found in lymphoma cells and many non-neoplastic cells. In addition, the expression of perforin was detected in almost all lymphoma cells. In the double stainings, lymphoma cells expressed both FasL and perforin. Based on these findings, both the perforin- and Fas-based pathway of the cytotoxic T/NK lymphoma cells are thus considered to play an important role in the clinical features.
Tissue damage is a common morphological feature in nasal T/NK cell lymphoma. The above findings therefore support the theory that tissue damage is due to both the cytotoxicity of T/NK lymphoma cells as well as to angiocentricity.
已证实T/自然杀伤(NK)细胞介导的细胞毒性存在两种分子机制,一种基于穿孔素,另一种基于Fas,且这两种系统均可诱导靶细胞产生细胞毒性。基于Fas的机制涉及转导分子Fas及其配体(FasL)。此外,穿孔素和/或FasL也在细胞毒性T/NK细胞中表达。因此,本研究旨在探究鼻腔细胞毒性T/NK淋巴瘤细胞的Fas和穿孔素途径。
采用免疫组织化学染色方法分析了8例鼻腔淋巴瘤患者。2例为CD3+ CD56+(T/NK细胞)型,6例为CD3- CD56+(NK细胞)型。所有病例经原位杂交均显示有爱泼斯坦-巴尔病毒基因组。此外,所有病例均显示有TIA-1(GMP-17)的表达,TIA-1是细胞毒性T细胞和NK细胞的标志物。FasL在大多数淋巴瘤细胞和一些组织细胞中表达,而Fas在淋巴瘤细胞和许多非肿瘤细胞中发现。此外,几乎所有淋巴瘤细胞中均检测到穿孔素的表达。在双重染色中,淋巴瘤细胞同时表达FasL和穿孔素。基于这些发现,细胞毒性T/NK淋巴瘤细胞基于穿孔素和Fas的途径在临床特征中均被认为发挥重要作用。
组织损伤是鼻腔T/NK细胞淋巴瘤常见的形态学特征。因此,上述发现支持组织损伤是由于T/NK淋巴瘤细胞的细胞毒性以及血管中心性这一理论。