Immunopathological study on cytokine-producing cells in acute oral mucosal graft-versus-host disease

急性口腔粘膜移植物抗宿主病细胞因子产生细胞的免疫病理学研究

• 批准号: 11671876
• 负责人: OHNO Jun
• 金额: $ 1.47万
• 依托单位: Meikai University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 1999
• 资助国家: 日本
• 起止时间: 1999 至 2000
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-11671876/
• 关键词: ORAL MUCOSAL GVHD; ICAM-1; CYTOKINES; RT-PCR; IMMUNOHISTOCHEMISTRY; CYTOTOXIC T CELL; INTERFERON-GAMMA; RATS

The results obtained were divided into two parts ; 1) roles of cytokines in the induction of acute oral mucosal GVHD, and 2) dynamics of immunocompetent cells, containg cytokine-producing cells. By the RT-PCR methods, both interferon-gamma (IFN) and tumor necrosis factor-alpha (TNF) mRNAs were expressed in the lesional sites at very early stage of oral lesions. The expression of those cytokines was concomitant with immunohistochemical expression of ICAM-1 on the epithelial keratinocytes (KC). These results suggest that local production of IFN and TNF may be responsible for the induction of ICAM-1 expression on KC.Futhermore, the fact that ICAM-1 expression on KC regulates to an infiltration of cytotoxic T cells (CD8-positive cells) into the epithelium, was proved by Stamper-Woodruff binding assay. Of the cytokine-producing cells, we supeculate that NK-like cells and macrophages may be resposible for the production of IFN and TNF, respectively, by in situ hybridization. From these evidences, 'we conclude that NK-like cells and macrophages play important roles in the initiation of acute oral mucosal GVHD.The cytokines produced by those cells may regulate the epitheliotropism of cytotoxic T cell by LFA-1/ICAM-1 binding pathway.

结果分为两部分：1)细胞因子在急性口腔粘膜移植物抗宿主病诱导中的作用；2)免疫活性细胞的动态变化，包括细胞因子产生细胞。逆转录-聚合酶链式反应显示，干扰素-γ和肿瘤坏死因子-α在口腔病变早期皮损部位均有表达。这些细胞因子的表达伴随着上皮角质形成细胞(KC)ICAM-1的免疫组织化学表达。这些结果表明，局部产生的干扰素和肿瘤坏死因子可能是诱导KC表面ICAM-1表达的原因。Stamper-Woodruff结合实验证实，KC表面ICAM-1的表达调节细胞毒性T细胞(CD8阳性细胞)向上皮细胞的渗透。在产生细胞因子的细胞中，我们推测NK样细胞和巨噬细胞可能通过原位杂交分别负责产生干扰素和肿瘤坏死因子。这些证据表明，NK样细胞和巨噬细胞在急性口腔粘膜GVHD的发病过程中起重要作用，其产生的细胞因子可能通过LFA-1/ICAM-1结合途径调节细胞毒性T细胞的嗜上皮性。

项目成果

J.Ohno: "Basic research and its possible application to oral cancer therapy. Part 2 : GVHD and cancer therapy"Hosp.Dent.(Tokyo). 12 (in Japanese). 71-84 (2000)

J.Ohno：“基础研究及其在口腔癌治疗中的可能应用。第 2 部分：GVHD 和癌症治疗”Hosp.Dent.（东京）。

大野純 他: "急性GVHDの口腔粘膜破壊機序におけるICAM-1の役割."消化器と免疫. 36. 113-116 (1999)

Jun Ohno 等人：“ICAM-1 在急性 GVHD 口腔粘膜破坏机制中的作用”36. 113-116 (1999)。