Nikkels Arjen F, Sadzot-Delvaux Catherine, Piérard Gérald E
Department of Dermatopathology, University of Liège, Liège, Belgium.
Am J Dermatopathol. 2004 Feb;26(1):27-32. doi: 10.1097/00000372-200402000-00005.
Downregulation of major histocompatibility complex (MHC) class I, MHC-II, and intercellular adhesion molecule 1 (ICAM-1) expression in infected cell lines allows some viruses to escape host immunity. In skin lesions of varicella zoster virus (VZV), MHC-II transcripts were demonstrated in keratinocytes around vesicles, but not in VZV-infected cells. Whether other immunoevasive mechanisms are present during herpes zoster (HZ) is not yet elucidated. The aim of the study was to disclose the temporal immunohistochemical expression of immune escape mechanisms during HZ. Sequential skin biopsies were performed in 5 HZ patients. VZV IE63, CD1a, CD3, CD4, CD8, CD56, CD68, L1, HLA-DR, HLA-ABC, interleukin (IL)-6, IL-10, interferon gamma (IFNgamma), tumor necrosis factor alpha (TNFalpha), and ICAM-1 expressions were assessed on frozen sections using immunohistochemistry. Controls consisted of normal skin, herpes simplex virus (HSV) skin infections, and other distinct bullous skin diseases. HLA-DR and ICAM-1 expressions were not observed in VZV- and HSV-infected keratinocytes, contrasting with their upregulation in the surrounding epidermis and inside nonviral blisters. However, HLA-ABC expressions were not inhibited in VZV-infected keratinocytes. Furthermore, the CD4/CD8 ratio remained unmodified during the infection evolution, and this ratio was variable among patients. Increased IFNgamma, TNFalpha, and IL-6 expressions were present, but IL-10 expression only increased in later stages. In contrast to in vitro MHC-I and MHC-II downregulation, VZV infection is related to MHC-II but not MHC-I expression on infected keratinocytes. The absence of ICAM-1 expression on infected keratinocytes may reduce their antigen presentation capacities to LFA-1 ligand-bearing T cells. This may represent another VZV-associated immune escape mechanism. Increased IFNgamma, TNFalpha, and IL-6 expressions suggest a TH1 profile.
主要组织相容性复合体（MHC）I类、MHC-II类以及细胞间黏附分子1（ICAM-1）在受感染细胞系中的表达下调，使一些病毒能够逃避宿主免疫。在水痘带状疱疹病毒（VZV）感染的皮肤损伤中，水疱周围的角质形成细胞中有MHC-II转录本，但在VZV感染的细胞中未检测到。目前尚不清楚带状疱疹（HZ）期间是否存在其他免疫逃避机制。本研究的目的是揭示HZ期间免疫逃避机制的时间性免疫组化表达情况。对5例HZ患者进行了连续的皮肤活检。采用免疫组化方法在冰冻切片上评估VZV IE63、CD1a、CD3、CD4、CD8、CD56、CD68、L1、HLA-DR、HLA-ABC、白细胞介素（IL）-6、IL-10、干扰素γ（IFNγ）、肿瘤坏死因子α（TNFα）以及ICAM-1的表达。对照组包括正常皮肤、单纯疱疹病毒（HSV）皮肤感染以及其他不同的大疱性皮肤病。在VZV和HSV感染的角质形成细胞中未观察到HLA-DR和ICAM-1的表达，这与它们在周围表皮和非病毒水疱内的上调形成对比。然而，HLA-ABC的表达在VZV感染的角质形成细胞中未受抑制。此外，在感染过程中CD4/CD8比值保持不变，且该比值在患者之间存在差异。IFNγ、TNFα和IL-6的表达增加，但IL-10的表达仅在后期增加。与体外MHC-I和MHC-II下调不同，VZV感染与受感染角质形成细胞上的MHC-II表达有关，而与MHC-I表达无关。受感染角质形成细胞上ICAM-1表达的缺失可能会降低它们向携带LFA-1配体的T细胞呈递抗原的能力。这可能代表了另一种与VZV相关的免疫逃避机制。IFNγ、TNFα和IL-6表达的增加提示了TH1型免疫反应。
