Polarity of helper T cell subsets represents disease nature and clinical course of experimental autoimmune myocarditis in rats
Polarity of helper T cell subsets represents disease nature and clinical course of experimental autoimmune myocarditis in rats
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DOI：
10.1111/j.1365-2249.2003.02312.x
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发表时间：
2003-12-01
影响因子：
4.6
通讯作者：
Aizawa, Y
中科院分区：
文献类型：
--
作者：
Fuse, K;Kodama, M;Aizawa, Y
心肌炎的进展、缓解和复发的机制尚不清楚。为了阐明这些机制，我们重点研究了实验性自身免疫性心肌炎(EAM)大鼠疾病进展过程中外周血淋巴细胞辅助性T细胞1(Th1)/辅助性T细胞2(Th2)亚群的平衡和血清细胞因子水平。Lewis大鼠在第0天用心肌肌球蛋白免疫。分别于免疫后0、7、15、18、21、28、35、42、49、56天采集血样。我们用流式细胞仪分析了刺激外周血中产生干扰素(干扰素)-γ和/或白介素4(IL-4)的细胞百分比。采用双抗体夹心酶联免疫吸附试验检测血清干扰素-γ、白介素2、白介素6、白介素10水平。0、15、28、56天EAM中Th1/Th2亚群百分比分别为2.5+/-0.5/0.5+/-0.1%、19.4+/-3.2/1.6+/-0.3%、2.0+/-0.5/22.1+/-5.7%和3.0+/-0.4/1.7+/-0.3%。血清Th1细胞因子、干扰素-γ和IL-2水平在急性期(第15-18天)显著升高，在恢复期即刻下降。而血清Th2细胞因子、IL-10水平在恢复期早期(24-30天)显著升高。这些结果提示，急性心肌炎的诱发可能与全身Th1优势有关，而恢复则与全身Th2极性有关。因此，外周血T细胞Th1/Th2平衡的分析可能有助于心肌炎和心肌炎后扩张型心肌病患者的病情监测。
The mechanisms of progression, remission and relapse of myocarditis remain unclear. To clarify these mechanisms, we focused on T helper-1 (Th1)/T helper-2 (Th2) subsets balance of peripheral lymphocytes and serum cytokine levels during disease progression in rats with experimental autoimmune myocarditis (EAM). Lewis rats were immunized with cardiac myosin on day 0. Blood samples were collected on days 0, 7, 15, 18, 21, 28, 35, 42, 49 and 56 following immunization. We examined percentages of interferon (IFN)-gamma and/or interleukin (IL)-4 producing cells in stimulated peripheral CD4-positive lymphocytes using flow cytometry analysis. Serum IFN-gamma, IL-2, IL-6 and IL-10 levels were measured by enzyme-linked immunosorbent assay (ELISA). The percentage of Th1/Th2 subsets in EAM on days 0, 15, 28 and 56 were 2.5+/-0.5/0.5+/-0.1%, 19.4+/-3.2/1.6+/-0.3%, 2.0+/-0.5/22.1+/-5.7% and 3.0+/-0.4/1.7+/-0.3%, respectively. Serum levels of Th1 cytokines, IFN-gamma and IL-2 significantly increased in the acute phase (from day 15-18) and immediately decreased in the early recovery phase. On the other hand, serum levels of Th2 cytokine, IL-10 significantly increased in the early recovery phase (from day 24-30). These results suggest that induction of acute myocarditis might be associated with systemic Th1 dominance, while recovery is related to systemic Th2 polarity. Thus, analysis of Th1/Th2 balance in peripheral T cells may be useful in disease monitoring in patients with myocarditis and postmyocarditic dilated cardiomyopathy.