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

• 批准号: 10203783
• 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
• 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/10203783
• 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; Immunology; 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; 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

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） 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，并已开发出一种增强其功能的策略 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 使用细胞预防肾移植后从头产生移植后同种抗体和AMR 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。