研究预防和治疗急性抗体介导的肾移植排斥反应的新型细胞疗法-猫眼课题宝

研究预防和治疗急性抗体介导的肾移植排斥反应的新型细胞疗法

批准号：

10436921

负责人：

GINNY L BUMGARDNER

金额：

$53.44万

依托单位：

OHIO STATE UNIVERSITY

依托单位国家：

美国

项目类别：

财政年份：

2019

资助国家：

美国

项目状态：

已结题

起止时间：

2019-07-01 至 2024-06-30

来源：

https://reporter.nih.gov/project-details/10436921

关键词：

Acute Adoptive Cell Transfers Adoptive Transfer Allograft Tolerance Allografting Antibodies Antibody Formation Antibody Therapy Antigens Attenuated Autoimmunity Automobile Driving B-Lymphocytes BLR1 gene Biological Assay CD4 Positive T Lymphocytes CD8-Positive T-Lymphocytes CD8B1 gene Cantor Cell Communication Cell Therapy Cell Transplantation Cells Cellular immunotherapy Chronic Clinical Clinical Data Clinical Research Cytometry Data Development Dose Down-Regulation FOXP3 gene Foundations Functional disorder Genetic Graft Rejection Hepatocyte Hepatocyte transplantation Histopathology Human Humoral Immunities Hypersensitivity IgE Immune Immunosuppression Immunosuppressive Agents Immunotherapy In Vitro Incidence Interferon Type II Interleukin-10 Interleukin-2 Islets of Langerhans Transplantation Isoantibodies Kidney Kidney Failure Kidney Transplantation Lymphoid Mediating Microsurgery Modeling Mus Organ Transplantation Pathology Patients Phenotype Production Publishing Qa-1 Antigen Regulatory T-Lymphocyte Reporting Research Research Personnel Risk Role Severities Skin Transplantation Solid Structure of germinal center of lymph node T-Cell Depletion T-Lymphocyte Subsets Testing Tissues Transplant Recipients Transplantation Transplantation Immunology Tumor Immunity Virus Diseases antibody-mediated rejection autoreactivity cancer vaccination cytotoxic donor-specific antibody efficacy testing imaging approach immunoregulation improved in vivo innovation isoimmunity kidney allograft liver allograft mouse model novel pathogen perforin peripheral blood post-transplant pre-clinical preclinical study preservation prevent programmed cell death protein 1 prospective response targeted agent trafficking transplant model treatment choice vaccination strategy

中文摘要

翻译

项目摘要已知移植特异性抗体（同种抗体）介导急性抗体介导的排斥反应（AMR）并且也对肾移植物的长期存活产生负面影响。我们小组发现了一个新的调节性CD 8 + T细胞亚群抑制移植后同种抗体的产生。我们称这些抗体抑制CD 8 + T细胞作为CD 8 + TAb-supp细胞，并已开发出一种策略，以提高其在体内发育中，将它们表型与其他同种异体致敏的CD 8 + T细胞区分开，并在体外评估它们的表型。和体内功能。在目标1中，我们将进行临床前研究，以调查CD 8 + TAb-supp 细胞预防肾移植后新生移植后同种抗体和AMR的发展，复制人肾中观察到的AMR组织病理学的鼠肾移植模型移植接受者在目标2中，我们将进行临床前研究，以调查过继细胞免疫的功效。用CD 8 + TAb-supp细胞治疗AMR并延长肾移植功能和存活。我们的研究该团队汇集了具有临床移植，移植免疫学，显微外科学专业知识的研究人员和肾脏组织病理学。

英文摘要

Project Summary Transplant specific antibodies (alloantibodies) are known to mediate acute antibody-mediated rejection (AMR) after kidney transplant and also negatively impact long-term kidney allograft survival. Our group discovered a novel regulatory CD8+ T cell subset which suppresses alloantibody production posttransplant. We refer to these antibody suppressor CD8+ T cells as CD8+ TAb-supp cells and have developed a strategy to enhance their in vivo development, distinguish their phenotype from other alloprimed CD8+ T cells and assess their in vitro and in vivo function. In Aim 1 we will perform pre-clinical studies to investigate the efficacy of CD8+ TAb-supp cells to prevent the development of de novo post-transplant alloantibody and AMR after kidney transplant using a murine model of kidney transplant which reproduces the histopathology of AMR observed in human kidney transplant recipients. In Aim 2 we will perform pre-clinical studies to investigate the efficacy of adoptive cellular therapy with CD8+ TAb-supp cells to treat AMR and prolong kidney transplant function and survival. Our research team assembles investigators with expertise in clinical transplantation, transplant immunology, microsurgery and kidney histopathology.

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