CELLULAR POPULATIONS MEDIATING SKIN ALLOGRAFT REJECTION

介导皮肤同种异体移植排斥的细胞群

• 批准号: 3770383
• 负责人: A S ROSENBERG
• 金额: --
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/3770383
• 关键词: CD8 molecule; MHC class I antigen; MHC class II antigen; antibody; athymic mouse; cell population study; cytokine; cytotoxic T lymphocyte; helper T lymphocyte; homologous transplantation; liposomes; macrophage; phenotype; skin transplantation; transplant rejection

This project involves 1) ongoing studies assessing the role of CD4+ T cells in rejection of MHC class I disparate skin grafts 2) new studies that assess the role of the macrophage in skin allograft rejection, and 3) new studies assessing the role of primed lymphocyte populations in graft rejection. 1) To assess the role of CD4+ T cells in rejection of MHC class I disparate Kb mutant skin grafts, two different types of experiments have been performed: antibody depletion studies in which thymectomized or non- thymectomized mice were depleted of CD4+ T cells in vivo by injection of antibody and engrafted with MHC class I disparate skin and adoptive transfer studies in which graded numbers of CD4+ T cells are added to athymic nude mice reconstituted with CD8+ T cells. Both of these approaches have yielded compatible information pointing to inhibition of MHC class I disparate graft rejection by CD4+ T cells. Further studies assessing the specificity of the effect are planned as well as extension of these studies to non-Kb mutant MHC class I disparate skin grafts. 2) Macrophages are present in abundance in skin grafts rejected across MHC class II and minor-histocompatibility barriers but not in those rejected across MHC class I barriers. Although the activity of macrophages in the rejection process has not been defined, it is possible that they contribute in a multiplicity of ways, including enhanced antigen presentation, elaboration of cytokines and other factors, and direct induction of tissue damage. Studies to date indicate that macrophages present in rejecting MHC class II disparate grafts are activated and that cytokines which may be of macrophage origin (IP-10 and IL-1) are elaborated. Further studies are planned to establish the source of the cytokines. Additional studies in which macrophages are depleted by toxic liposomes will most directly assess their role in rejection across differing histocompatibility disparities. 3) Although the cellular populations mediating allograft rejection have begun to be understood for primary rejection responses, almost nothing is known about the cellular mechanisms and interactions involved in secondary (primed) responses. Studies in which the specificity of the effector mechanisms, the phenotype of the cellular populations infiltrating rejecting grafts, and the cytokine activity present in rejecting grafts have commenced.

该项目涉及1）正在进行的研究，评估CD 4 + T细胞的作用， 细胞在MHC I类不同皮肤移植物排斥反应中的作用2）新研究 评估巨噬细胞在皮肤移植排斥反应中的作用，以及3） 评估预处理淋巴细胞群在移植物中作用的新研究 排斥反应 1)探讨CD 4 + T细胞在MHC I类分子排斥反应中的作用 不同的Kb突变皮肤移植，两种不同类型的实验， 进行的：抗体耗竭研究，其中胸腺切除或非胸腺切除 胸腺切除的小鼠通过注射 抗体，并与MHC I类不同的皮肤和过继 转移研究，其中将分级数量的CD 4 + T细胞加入到 用CD 8 + T细胞重建的无胸腺裸鼠。 这两 方法产生了一致的信息，指出抑制 由CD 4 + T细胞引起的MHC I类异种移植物排斥。 进一步研究 计划评估影响的特异性以及扩展 非Kb突变型MHC I类异种皮肤移植的研究。 2)在皮肤移植物中大量存在巨噬细胞， MHC II类和次要组织相容性屏障，但在那些 通过MHC I类屏障被排斥。 虽然活动的 巨噬细胞在排斥反应过程中的作用尚未确定，这是可能的。 它们以多种方式起作用，包括增强抗原 细胞因子和其他因子的呈递、加工，以及直接 诱导组织损伤。 迄今为止的研究表明， 存在于排斥MHC II类不同移植物中的抗原被激活， 可能是巨噬细胞来源的细胞因子（IP-10和IL-1）是 详细说明。 计划进行进一步的研究，以确定 细胞因子 其他研究中，巨噬细胞被有毒物质耗尽 脂质体将最直接地评估它们在排斥反应中的作用， 不同的组织相容性差异。 3)尽管介导同种异体移植排斥反应的细胞群 开始被理解为主要的排斥反应，几乎没有什么是 已知的细胞机制和相互作用参与继发性 （primed）响应。 效应子的特异性 机制，浸润细胞群体的表型 排斥性移植物和排斥性移植物中存在的细胞因子活性 已经开始了。