The in Vivo Significance of T Cells in Coxsackievirus B3 Myocarditis

T 细胞在柯萨奇病毒 B3 心肌炎中的体内意义

• 批准号: 01570478
• 负责人: KISHIMOTO Chiharu
• 金额: $ 1.34万
• 依托单位: Toyama Medical & Pharmaceutical University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for General Scientific Research (C)
• 财政年份: 1989
• 资助国家: 日本
• 起止时间: 1989 至 1990
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-01570478/
• 关键词: Coxsackievirus B3; Myocarditis; Dilated Cardiomyopathy; T-lymphocytes; ウィルス性心筋炎; 拡張型心筋炎; 免疫学

Acute myocardial damage similar to that seen in human myocarditis occurs in BALB/c mice after infection with Coxsackievirus B3 (CB3) or Encephalo-Myocarditis Virus (EMV). To investigate the role of antigen-specific T cells in the pathogenesis of this disorder, we compared CB3 disease expression in T cell-deficient, athymic nude (nu/nu) mice, in heterozygote (nu+) mice with normal T cell function, and in nu/nu mice reconstituted with spleen cells from CB3- or EMV-infected nu/+mice. Acute myocarditis occurred in both nu/nu and nu/+ mice, Severe myocarditis, however, developed only in nu/+ and nu/nu/nu mice reconstituted with CB3-sensitized T cells, but not in those reconstituted with EMC-sensitized T cells. Myocardial virus titer and serum anti-CB3 antibody production were similar in nu/+ and nu/nu groups. Additionally, the presence of Thy 1.2 (pan T), Ly 1 (precursor of other T cell subsets), and Ly 2 (suppressor/cytotoxic T) positive cells was demonstrated in the myocardium in nu/+ and … More nu/nu mice reconstituted with CB3-sensitized T cells, but not with T cells sensitized by another virus, EMC. These results indicate that immature but antigen-specific T cells play a role in the pathogesis of ongoing myocarditis.To test the effects of interleukinー2 (IL-2) upon CB3 myocarditis recombinant human IL-2, 5x10^4U, was administered subcutaneously daily starting on day O and on day 7 for 7 days, respectively. The treated groups were compared to infected controls. As a result, IL-2 has differential effects upon CB3 myocarditis ; IL-2 has the potency to limit CB3 myocarditis in the acute viremic stage, but it aggravates the course and the severity of the disease in the subacute a viremic stage by T cell activation. Also, FK-506, a novel immunosuppressant, induced immunosuppression in CB3 myocarditis, associated with a high mortality, notwithstanding the reduction of cardiac pathology.In addition, Fc receptor-mediated CB3 infection in vitro and in vivo was demonstrated in this murine model. Less

BALB/c小鼠感染柯萨奇病毒B3（CB 3）或脑心肌炎病毒（EMV）后，出现与人类心肌炎相似的急性心肌损伤。为了研究抗原特异性T细胞在这种疾病的发病机制中的作用，我们比较了T细胞缺陷的无胸腺裸小鼠（nu/nu），具有正常T细胞功能的杂合子（nu+）小鼠，以及用来自CB 3或EMV感染的nu/+小鼠的脾细胞重建的nu/nu小鼠中CB 3疾病的表达。nu/nu和nu/+小鼠均发生急性心肌炎，但严重心肌炎仅发生在用CB 3致敏的T细胞重建的nu/+和nu/nu/nu小鼠中，而不发生在用EMC致敏的T细胞重建的小鼠中。心肌病毒滴度和血清抗CB 3抗体的产生在nu/+和nu/nu组中相似。此外，在nu/+和nu/+的心肌中证实了Thy 1.2（pan T）、Ly 1（其他T细胞亚群的前体）和Ly 2（抑制/细胞毒性T）阳性细胞的存在。 ...更多信息 nu/nu小鼠用CB 3致敏的T细胞重建，但不用另一种病毒EMC致敏的T细胞重建。为了检测白细胞介素2（IL-2）对CB 3心肌炎的作用，分别从第0天和第7天开始每天皮下注射重组人IL-2，5 × 104 U，持续7天。将治疗组与感染对照组进行比较。结果，IL-2对CB 3心肌炎具有不同的作用; IL-2具有在急性病毒血症阶段限制CB 3心肌炎的效力，但它通过T细胞活化在亚急性病毒血症阶段加重疾病的病程和严重程度。此外，FK-506，一种新的免疫抑制剂，诱导免疫抑制CB 3心肌炎，与高死亡率，尽管减少心脏病理。此外，Fc受体介导的CB 3感染在体外和体内在这个小鼠模型中得到证实。少

项目成果

CHIHARU KISHIMOTO et al.: "Immunological mechanisms in experimental coxsakievirus B3 mycarditis in mice" Japanese Circulation Journal.

CHIHARU KISHIMOTO 等人：“小鼠实验性柯萨奇病毒 B3 心肌炎的免疫学机制”日本循环杂志。

CHIHARU KISHIMOTO et al.: "Antibodyーenhanced infection by coxsackievirus B3 via Fc receptor in vitro and in vivo:A possible mechanism of chronic active myocarditis" Circulation.

CHIHARU KISHIMOTO 等人：“体外和体内柯萨奇病毒 B3 通过 Fc 受体增强抗体感染：慢性活动性心肌炎的可能机制”循环。

CHIHARU KISHIMOTO et al.: "The in vivo significance of T cells in the development of coxsackievirus B3 myocarditis" Science.

CHIHARU KISHIMOTO 等人：“T 细胞在柯萨奇病毒 B3 心肌炎发展中的体内意义”《科学》。

岸本 千晴,篠山 重威,落合 宏: "免疫学的心筋細胞障害 シンポジウムII「心筋細胞障害の成因」" Japanese Circulation Journal. 54(Suppl 1). 47- (1990)

Chiharu Kishimoto、Shigetake Shinoyama、Hiroshi Ochiai：“免疫学心肌细胞损伤研讨会 II“心肌细胞损伤的原因”日本循环杂志。54（增刊 1）。47-（1990）

YUJI HIRAOKA et al.: "The effects of FKー506,a nover and potent immunoーsuppressant ,upon murine coxsackievirus B3 myocarditis" Journal of Antibiotics.

YUJI HIRAOKA 等人：“FK-506（一种新颖且有效的免疫抑制剂）对小鼠柯萨奇病毒 B3 心肌炎的影响”《抗生素杂志》。