Effect of aging on mucosal immune-defense of intestine

衰老对肠道粘膜免疫防御的影响

• 批准号: 03670347
• 负责人: ITO Masafumi
• 金额: $ 1.34万
• 依托单位: Yamagata 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: 1991
• 资助国家: 日本
• 起止时间: 1991 至 1993
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-03670347/
• 关键词: aging; Peyer's patch; immune function; T cell line; 加齢; 腸管粘膜防御機構; インターロイキン2

The research project was established by Dr. Ajitsu, previous head investigator, adn focused on whether the findings in murine model for aging (1) are available for human aging. We have investigated the dysfunction of intestinal immunity in aged persons by comparing IL-2 production of long-term cultured T cell lines derived from ileal mucosa between aged and young group. Utilizatin of long-term T cell lines made possible repeated experiments in our laboratory where there was few volunteers donating ileal mucosa.Ajitsu and Takahashi reported tha tIL-2 production by ileal mononuclear cells in response to mitogen was decreased in aged group (2). In our previous study using few ileal T cell lines lower production of IL-2 was observed in aged group than that in young group. However, recent study using more than 8 T cell lines showed that there was no significant difference in IL-2 production between aged group and control. We had a similar result in the study of patients with ulcerative colitis in which there was no significant difference in cytokines production by T cell lines derived from colonic mucosa between patients with ulcerative colitis and normal control (3).These results suggest that utilization of long term T cell lines is not suitable for the snalysis of immune dysfunction in aging because only T cells adapted in in -vitro condition could grow, thus, different approaches reflecting in-vivo situation should be made. We think that an analysis of expression of mRNA in Peyer's patch T cells using in-situ hybridization technique may be useful for the extension of this study.

该研究项目是由前首席研究员Ajitsu博士建立的，重点是小鼠衰老模型中的发现是否可用于人类衰老。本研究通过比较老年人和青年人回肠黏膜T细胞系长期培养产生IL-2的能力，探讨老年人肠道免疫功能障碍。长期T细胞系的使用使得在我们实验室中进行重复实验成为可能，因为很少有志愿者捐献回肠粘膜。Ajitsu和Takahashi报道，在老年组中，回肠单个核细胞响应于有丝分裂原产生的tIL-2减少（2）。在我们以前的研究中，用少量的回肠T细胞系观察到老年组IL-2的产生低于年轻组。然而，最近的研究表明，使用超过8个T细胞系的IL-2的产生在老年组和对照组之间没有显著差异。我们在溃疡性结肠炎患者的研究中也得到了类似的结果，其中溃疡性结肠炎患者和正常对照之间结肠粘膜来源的T细胞系的细胞因子产生没有显著差异（3）。这些结果表明，利用长期T细胞系不适合分析衰老中的免疫功能障碍，因为只有适应体外条件的T细胞才能生长，因此，应采用不同的方法来反映体内情况。我们认为，使用原位杂交技术分析派伊尔氏结T细胞的mRNA表达可能有助于本研究的扩展。

项目成果

S.AJITSU,T.Takahashi,M.Ito,H.Takeda,M.Ishikawa: "Effect of aging on T cell interaction in Peyeis Patch." Frontiers of Mucosal Immunology.Vol.1. 443-446 (1991)

S.AJITSU、T.Takahashi、M.Ito、H.Takeda、M.Ishikawa：“衰老对 Peyeis 斑块中 T 细胞相互作用的影响。”

Ito M., Fuyama S., Arai S., Hirata S., Ajitsu S.and Takahashi T.: "functional analysis of colonic T cells derived from patients with ulcerative colitis" Digestive organ and Immunology. 26. 41-45 (1992)

Ito M.、Fuyama S.、Arai S.、Hirata S.、Ajitsu S.和 Takahashi T.：“溃疡性结肠炎患者来源的结肠 T 细胞的功能分析”消化器官和免疫学。

Kawanishi H and Ajitsu S: "Correction of antigen-specific T cell defects in aged murine gut-associated tissures,an immune---" Eur J Immunol.21. 2907-2914 (1991)

Kawanishi H 和 Ajitsu S：“衰老小鼠肠道相关组织中抗原特异性 T 细胞缺陷的校正，免疫——”Eur J Nutrition.21。

Kawanshi H and Ajitsu S.: "Correctin of antigen-specific T cell defects in aged murine gut-associated lymphoid tissues andimmune intervention by combined adoptive transfer ofan antigen-specific immunoregulatory CD4 T cell subset and interleukin 2 administ

Kawanshi H 和 Ajitsu S.：“通过抗原特异性免疫调节性 CD4 T 细胞亚群和白细胞介素 2 联合过继转移来纠正老年小鼠肠道相关淋巴组织中的抗原特异性 T 细胞缺陷和免疫干预

伊藤真文,平田慎也,安日新 他: "潰瘍性大腸炎患者由来大腸粘膜T細胞の機能的解析" 消化器と免疫. 26. 41-45 (1992)

Masafumi Ito、Shinya Hirata、Shin Abi 等：“来自溃疡性结肠炎患者的结肠粘膜 T 细胞的功能分析”胃肠道和免疫学 26. 41-45 (1992)。