Cell-mediated immune cardiocyte injury in viral myocarditis of mice and patients.
Cell-mediated immune cardiocyte injury in viral myocarditis of mice and patients.
复制标题
小鼠和患者病毒性心肌炎中细胞介导的免疫心肌细胞损伤。
DOI：
--
复制
发表时间：
1989
期刊：
影响因子：
--
通讯作者：
K. Kawamura
中科院分区：
文献类型：
--
作者：
H. Deguchi;Y. Kitaura;T. Hayashi;M. Kotaka;K. Kawamura
本文通过观察和分析C_3 H/He小鼠和人病毒性心肌炎心肌细胞、T细胞、B细胞、自然杀伤（NK）细胞和巨噬细胞之间的相互作用，探讨了病毒性心肌炎心肌细胞损伤的细胞免疫机制。用免疫组织化学方法，对科萨基B3病毒性心肌炎小鼠心肌中的T细胞（Thy 1.2）、Th/i（Lyt 1+）、Tc/s（Lyt 2+）、B（IG+）和去唾液酸GM 1+细胞进行了鉴定。在心肌炎的急性期，去唾液酸GM 1+（主要是NK）细胞占主导地位的泛T细胞，并在第9天达到峰值。然后，Pan T细胞在第14天达到峰值。第5天T4/T8（Lyt 1+/Lyt 2+）比值为1.3 +/- 0.5，第14天达到峰值9.1 +/- 3.6，Lyt 1+细胞增加。此后，NK细胞和T细胞逐渐减少，甚至在3个月和12个月后仍可以在纤维化灶中看到。B细胞非常稀少，无法进行定量评价。电子显微镜检查显示，巨噬细胞与Th/i细胞、靶心肌细胞和较不常见的B细胞密切接触; Tc/s和NK细胞偶尔也与明显存活或退化的心肌细胞结合。一些淋巴细胞位于解离的闰盘的加宽的细胞间隙中，并且在一些心肌细胞的胞浆内加宽的界限中（empipolesis）。结果提示，在心肌炎急性期，NK细胞启动反应，致敏的细胞毒性T细胞和活化的巨噬细胞通过与靶细胞的密切接触，巨噬细胞、Th/i细胞和少量B细胞的密切接触，以及T_4/T_8比值的升高，可能促进了复杂免疫网络的调节，加重了细胞介导的损伤。在慢性期，残留但有活性的NK和细胞毒性T细胞可维持细胞毒性。在从8例病毒性或特发性心肌炎患者从临床发病后3至48天获得的心肌内膜活检中，常规电子显微镜显示心肌细胞，巨噬细胞和淋巴细胞之间的实际接触。在我们的小鼠模型中，一些淋巴细胞已emperipolesed在心肌细胞或位于解离的闰盘的加宽的空间。在这8例患者中的4例中，免疫组化证实了Leu 2a+ Tc/s、Leu 3+ Th/i和Leu 7+细胞的浸润，并且在肌内膜活检物中T4/T8比值在0.1至3.8之间变化很大。（400字处截断摘要）
The cellular immune mechanism of cardiocyte injury in viral myocarditis was investigated by observing and analyzing the interactions among cardiocytes, T cells, B cells, natural killer (NK) cells and macrophages in situ in the myocardium of our murine model (C3H/He mice) and of human patients. In murine coxsackie B3 virus myocarditis, lymphocyte subsets were identified by light and electron microscopic immunohistochemical techniques with antibodies against specific antigens of pan T (Thy 1.2), helper/inducer T (Th/i) (Lyt 1+), cytotoxic/suppressor T (Tc/s) (Lyt 2+), B (Ig+) and asialo GM1+ cells in the myocardium. In the acute phase of myocarditis, asialo GM1+ (mostly NK) cells predominated over pan T cells and peaked on day 9. Pan T cells then reached a peak on day 14. The T4/T8 (Lyt 1+/Lyt 2+) ratio was 1.3 +/- 0.5 on day 5 and reached a peak of 9.1 +/- 3.6 with an increase of Lyt 1+ cells on day 14. Thereafter, NK cells and T cells gradually decreased and could still be seen in fibrotic foci even 3 and 12 months later. B cells were so scarce that no quantitative evaluation could be made. Electron microscopy revealed that macrophages were in close contact with Th/i cells, target cardiocytes and less commonly, B cells; Tc/s and NK cells also occasionally conjugated with apparently viable or degenerated cardiocytes. Some lymphocytes were located in widened intercellular spaces of dissociated intercalated discs, and in intracytoplasmic widened confines of some cardiocytes (emperipolesis). These results suggest that in the acute phase of myocarditis, NK cells initiate the reaction, and then sensitized cytotoxic T cells and activated macrophages aggravate cell-mediated injury by their close contacts with target cardiocytes; close contacts among macrophages; Th/i cells and a few B cells, and the increased T4/T8 ratio may facilitate regulation of the complex immune network; in the chronic phase, residual but active NK and cytotoxic T cells may sustain cytotoxicity. In the endomyocardial biopsies obtained from 8 patients with viral or idiopathic myocarditis from 3 to 48 days after the clinical onset, conventional electron microscopy revealed actual contacts among cardiocytes, macrophages and lymphocytes. As in our murine model, some lymphocytes had emperipolesed in cardiocytes or were located in widened spaces of dissociated intercalated discs. In 4 of these 8 patients infiltration of Leu 2a+ Tc/s, Leu 3+ Th/i and Leu 7+ cells was identified immunohistochemically, and T4/T8 ratios varied widely from 0.1 to 3.8 in the endomyocardial biopsides.(ABSTRACT TRUNCATED AT 400 WORDS)