LIVER TRANSPLANTATION--THE ROLE OF DENDRITIC CELLS

肝移植——树突状细胞的作用

• 批准号: 2856784
• 负责人: Angus W Thomson
• 金额: $ 7.41万
• 依托单位: UNIVERSITY OF PITTSBURGH AT PITTSBURGH
• 依托单位国家: 美国
• 财政年份: 1998
• 资助国家: 美国
• 起止时间: 1998-05-01 至 1999-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2856784
• 关键词: MHC class II antigen; anergy; antibody; apoptosis; cadherins; cytokine; cytokine receptors; cytotoxic T lymphocyte; dendritic cells; extracellular matrix proteins; gene expression; heart transplantation; homologous transplantation; immune tolerance /unresponsiveness; immunoglobulins; immunosuppression; integrins; laboratory mouse; liver transplantation; phenotype; polymerase chain reaction; receptor binding; selectins; skin transplantation; transplantation immunology

DESCRIPTION: (Adapted from the applicant's abstract) It is noted that the orthotopic liver transplant model in mice results in virtually 100 percent tolerance and survival of recipients without need for immunosuppression and also results in transfer of dendritic cells systemically within the recipient. Progenitor dendritic cells are deficient in MHC Class II and stimulatory molecule expression and allostimulatory activity and can also prolong allograft survival in certain circumstances. These immunosuppressive properties of progenitor dendritic cells are controlled by both cytokines and by matrix interactions. Therefore the applicant hypothesizes that regulation of the expression of cell surface MHC antigens and T cell costimulatory molecules on dendritic cells determines their potential to induce tolerance and immunity. Three specific aims are proposed: I. Determine how cytokines and matrix proteins alter the phenotype and function of liver dendritic cells. II. Define the cellular and molecular mechanisms by which alterations in dendritic cell phenotype and function alter T cell responses in vitro. III. Establish the in vivo relevance of alterations in dendritic cell expression of co-stimulatory molecules by extending their observation that dendritic progenitors promote the survival of organ allografts.

描述：(改编自申请人的摘要)请注意， 小鼠原位肝移植模型结果几乎为100例 不需要的接受者的耐受性和存活率 免疫抑制和树突状细胞的转移 在接受者内部有系统地。祖树突状细胞是 MHC II类和刺激性分子表达不足 同种异体刺激活性，并可延长同种异体移植物存活时间。 在某些情况下。祖细胞的这些免疫抑制特性 树突状细胞受细胞因子和基质的双重调控 互动。因此，申请人假设对 细胞表面MHC抗原的表达与T细胞共刺激 树突状细胞上的分子决定了它们诱导 宽容和豁免权。提出了三个具体目标：一、确定 细胞因子和基质蛋白如何改变细胞的表型和功能 肝脏树突状细胞。二、明确细胞和分子机制 树突状细胞表型和功能的改变通过改变T细胞 细胞在体外的反应。三、建立在体内的相关性 共刺激分子对树突状细胞表达的影响 扩大了他们的观察，树突状祖细胞促进 同种异体器官移植的存活。