Verbeke C S, Wenthe U, Bergler W F, Zentgraf H
Pathology Institute, Faculty of Clinical Medicine, University of Heidelberg, Heidelberg, Germany.
Clin Exp Immunol. 2000 May;120(2):294-300. doi: 10.1046/j.1365-2249.2000.01181.x.
Infectious mononucleosis (IM), a manifestation of primary infection with EBV, is characterized by a massive expansion of the T cell population. In this study we examined this expanded T cell population regarding its EBV status, its proliferative and apoptotic activity, and its expression of apoptosis-related genes. Whereas previous studies were performed on ex vivo cultures or on peripheral blood, our investigations included in vivo analysis of IM tonsillectomy specimens (14 cases) by in situ hybridization for viral RNA (EBERs) combined with immunohistochemistry (IHC; CD3, CD45RO, CD20, CD79a, Ki-67, Bcl-2, Bax, Fas, FasL) and the TUNEL method. Of the EBER+ cells 50-70% showed expression of the B cell markers CD20/CD79a. The remainder of the EBER+ cells expressed neither B nor T cell antigens. No co-expression of EBERs and T cell antigens was detected in any of the specimens. In accordance with a high rate of apoptosis (up to 2.37%) within the expanded T cell population, Bcl-2 expression was drastically reduced and FasL expression remarkably increased. The levels of Bax and Fas expression showed no or moderate up-regulation. In conclusion, the massive expansion of IM T cells is not caused by EBV infection of these cells but merely represents an intense immune reaction. Through altered expression of Bcl-2/Bax and Fas/FasL, the activated T cells are subject to enhanced apoptosis while residing within the lymphoid tissue, which eventually allows the efficient silencing of this potentially damaging T cell response.
传染性单核细胞增多症(IM)是EB病毒原发性感染的一种表现,其特征为T细胞群体大量扩增。在本研究中,我们针对这一扩增的T细胞群体,检测了其EB病毒状态、增殖及凋亡活性,以及凋亡相关基因的表达。以往研究是在体外培养物或外周血上进行的,而我们的研究包括通过病毒RNA原位杂交(EBERs)结合免疫组织化学(IHC;CD3、CD45RO、CD20、CD79a、Ki-67、Bcl-2、Bax、Fas、FasL)和TUNEL法,对IM扁桃体切除标本(14例)进行体内分析。在EBER+细胞中,50 - 70%表达B细胞标志物CD20/CD79a。其余EBER+细胞既不表达B细胞抗原也不表达T细胞抗原。在任何标本中均未检测到EBERs与T细胞抗原的共表达。与扩增的T细胞群体内高凋亡率(高达2.37%)一致,Bcl-2表达显著降低,FasL表达显著增加。Bax和Fas表达水平无上调或仅有中度上调。总之,IM T细胞的大量扩增并非由这些细胞的EB病毒感染所致,而仅仅代表一种强烈的免疫反应。通过Bcl-2/Bax和Fas/FasL表达的改变,活化的T细胞在驻留于淋巴组织时会经历增强的凋亡,这最终使得这种潜在有害的T细胞反应得以有效沉默。