Investigating a Novel Cellular Therapy to Prevent and Treat Acute Antibody Mediated Kidney Transplant Rejection

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

基本信息

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
起止时间：
2019-07-01 至 2024-06-30
项目状态：
已结题

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

项目摘要

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.

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）肾脏移植后，还会对长期肾脏同种异体移植物的生存产生负面影响。我们的小组发现了一个新型的调节性CD8+ T细胞子群，可抑制移植后同抗体产生。我们指的是这些抗体抑制CD8+ T细胞作为CD8+ TAB-SUPP细胞，并制定了一种增强其策略在体内发育，将其表型与其他同种异体CD8+ T细胞区分开，并评估其体外和体内功能。在AIM 1中，我们将进行临床前研究以研究CD8+ TAB-SUPP的功效通过使用肾脏移植后移植后植物后植物后植物和AMR的发展细胞肾脏移植的鼠模型，该模型在人肾脏中观察到的AMR的组织病理学移植接受者。在AIM 2中，我们将进行临床前研究，以研究收养细胞的功效用CD8+ TAB-SUPP细胞治疗以治疗AMR并延长肾脏移植功能和存活。我们的研究团队组装研究人员具有临床移植，移植免疫学，显微外科手术方面的专业知识和肾脏组织病理学。