Qasim F J, Thiru S, Mathieson P W, Oliveira D B
Department of Medicine, Cambridge University School of Clinical Medicine, Addenbrooke's Hospital, UK.
J Autoimmun. 1995 Apr;8(2):193-208. doi: 10.1006/jaut.1995.0015.
Mercuric chloride (HgCl2) induces an autoimmune syndrome in the Brown Norway (BN) rat which includes widespread tissue injury. There is necrotizing leucocytoclastic vasculitis in the gut with maximal injury occurring 2 weeks after the start of HgCl2 injections. There is evidence that disease is driven by Th2-like cell (CD4+CD45RClow) activity and that Th1-like cells (CD4+CD45RChigh) may be protective. Using the established protocol of five injections of HgCl2 over 10 days, we have studied in greater detail the presence and extent of vasculitis and changes in T cell subsets from 12 h to 20 days after the first injection. Animals were killed at various time points and necropsies performed. Tissue injury was scored both macroscopically and histologically, with immunohistochemistry for T cell subsets. Flow cytometry was used to determine T cell subsets in peripheral blood, mesenteric lymph node (LN) and spleen. Tissue injury was seen as early as 24 h after the first injection of HgCl2. The size of lesions and extent of vasculitis increased over the next two weeks with partial resolution at day 20. We confirmed that of peripheral blood T cells in the BN rat, less than 20% were CD8+ and a similar proportion were CD4+CD45RChigh, but found that less than 75% of CD8+ T cells were CD45RChigh (in other strains of rat more than 90% CD8+ T cells are CD45RChigh). Within 48 h, HgCl2 caused a rise in the proportion of CD4+ T cells in spleen, LN and peripheral blood which then fell towards normal at peak tissue injury. The proportion of CD4+CD45RClow T cells rose in the first week, but subsequently fell, with reciprocal changes in CD4+CD45RChigh T cells. There was an increase in CD8+ T cells towards peak disease. The speed of onset of tissue injury suggests that cells other than T cells may be involved in the primary induction of vasculitis, although Th2-like cells may be important in further tissue injury and in B cell activation. The rise in CD8+ and Th1-like cells towards peak disease supports the hypothesis that they are involved in disease regulation.
氯化汞（HgCl2）可在棕色挪威（BN）大鼠中诱发自身免疫综合征，其中包括广泛的组织损伤。肠道中存在坏死性白细胞破碎性血管炎，在开始注射HgCl2后2周出现最大损伤。有证据表明，该疾病由Th2样细胞（CD4 + CD45RClow）的活性驱动，而Th1样细胞（CD4 + CD45RChigh）可能具有保护作用。使用在10天内进行5次HgCl2注射的既定方案，我们更详细地研究了血管炎的存在和程度以及首次注射后12小时至20天内T细胞亚群的变化。在不同时间点处死动物并进行尸检。通过宏观和组织学对组织损伤进行评分，并对T细胞亚群进行免疫组织化学分析。流式细胞术用于确定外周血、肠系膜淋巴结（LN）和脾脏中的T细胞亚群。在首次注射HgCl2后24小时就可见到组织损伤。在接下来的两周内，病变大小和血管炎程度增加，在第20天部分消退。我们证实，在BN大鼠的外周血T细胞中，不到20%是CD8 +，类似比例的是CD4 + CD45RChigh，但发现不到75%的CD8 + T细胞是CD45RChigh（在其他品系的大鼠中，超过90%的CD8 + T细胞是CD45RChigh）。在48小时内，HgCl2导致脾脏、LN和外周血中CD4 + T细胞比例上升，然后在组织损伤高峰期降至正常。CD4 + CD45RClow T细胞的比例在第一周上升，但随后下降，CD4 + CD45RChigh T细胞则出现相反变化。在疾病高峰期，CD8 + T细胞增加。组织损伤的发病速度表明，除T细胞外的其他细胞可能参与血管炎的初始诱导，尽管Th2样细胞可能在进一步的组织损伤和B细胞活化中起重要作用。在疾病高峰期CD8 +和Th1样细胞的增加支持了它们参与疾病调节的假设。
