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.

所获得的结果分为两个部分：1）细胞因子在急性口腔粘膜GVHD诱导中的作用，和2）免疫活性细胞（包括产生精氨酸的细胞）的动力学。通过RT-PCR方法，干扰素-γ（IFN）和肿瘤坏死因子-α（TNF）mRNA在口腔病变的非常早期的病变部位表达。这些细胞因子的表达与上皮角质形成细胞（KC）上ICAM-1的免疫组化表达同时进行。这些结果表明，局部产生的IFN和TNF可能是诱导KC表达ICAM-1的原因。Stamper-Woodruff结合试验证实，KC表达ICAM-1可调节细胞毒性T细胞（CD 8阳性细胞）向上皮细胞的浸润。在产生IFN的细胞中，我们推测NK样细胞和巨噬细胞可能分别通过原位杂交产生IFN和TNF。结论：NK样细胞和巨噬细胞在急性口腔黏膜GVHD的发生中起重要作用，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细胞的趋上皮性。

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)。