ENDOTHELIAL MODIFICATIONS THAT REDUCE T CELL ACTIVATION

减少 T 细胞激活的内皮修饰

基本信息

  • 批准号:
    2857824
  • 负责人:
  • 金额:
    $ 41.5万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    1994
  • 资助国家:
    美国
  • 起止时间:
    1994-01-01 至 2000-12-31
  • 项目状态:
    已结题

项目摘要

DESCRIPTION (Adapted from the Applicant's abstract): Cultured human and pig endothelial cells (ECs) can present MHC molecules directly to human T cells and can provide sufficient costimulatory signals such that activation of resting T cells results. In the current funding period, the investigators have shown that human peripheral blood adherent cells can activate resting naive and memory T cells, that human ECs can activate resting memory but not naive T cells, and that non-immune cell types (e.g. fibroblasts) are unable to activate resting T cells and can only restimulate activated T blasts. These differences arise from differences in costimulator molecules expressed by these various cell types. The investigators hypothesize that human ECs will function in vivo to initiate recall responses by presenting antigen to circulating memory T cells but fail to initiate primary immune reactions involving naive T cells. They further hypothesize that alterations in the costimulator molecules expressed by ECs will alter T cell activation in vitro and alter the outcome of immune reactions in vivo. In the renewal period the investigators propose to test these hypotheses in five specific aims. (1) The costimulator molecules on cultured human ECs will be altered by reducing LFA-3 (CD58), expressing transfected B7.1 (CD80) or B7.2 (CD86), blocking CD40, or pretreating with cytokines and the consequences for T cell subset activation will be assessed using in vitro assays (cytokine transcription and secretion, proliferation, differentiation and development of anergy); (2) Pig ECs, which express B7.2, will be compared to human ECs in the same assays and pig B7.2 will be analyzed when expressed in human ECs; (3) The role of costimulators (LFA-3, B7.1, B7.2, CD40) on ECs will be studied in a human peripheral blood lymphocyte-severe combined immunodeficient (huPBL-SCID) mouse model of vascularized human skin allograft rejection, developed by the investigators; (4) The huPBL-SCID mouse model will be extended to examine human T cell-pig EC interactions by engraftment of vascularized pig skin grafts; (5) New huPBL-SCID mouse models will be developed to examine human T cell interactions with human ECs that have been genetically modified to alter the expression of costimulator molecules. These experiments will (1) provide a test of the hypotheses; (2) test the concept that genetic alterations of ECs can alter the course of T cell-mediated injury in allografts, xenografts and other settings; and (3) develop new and useful in vivo models for evaluating the efficacy of immunosuppressive drugs, anti-human antibodies, and other therapeutic interventions on human immune responses.
描述(改编自申请人摘要):培养人和猪

项目成果

期刊论文数量(0)
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JORDAN S POBER其他文献

JORDAN S POBER的其他文献

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{{ truncateString('JORDAN S POBER', 18)}}的其他基金

Ex Vivo Nanoparticle Drug Delivery Targeted to Human Allograft Endothelium
针对人同种异体移植物内皮的体外纳米颗粒药物输送
  • 批准号:
    10783379
  • 财政年份:
    2023
  • 资助金额:
    $ 41.5万
  • 项目类别:
Assessment of immunogenicity and antigenicity of different human cell types in natural and 3D-printed allografts
评估天然和 3D 打印同种异体移植物中不同人类细胞类型的免疫原性和抗原性
  • 批准号:
    10353416
  • 财政年份:
    2021
  • 资助金额:
    $ 41.5万
  • 项目类别:
Assessment of immunogenicity and antigenicity of different human cell types in natural and 3D-printed allografts
评估天然和 3D 打印同种异体移植物中不同人类细胞类型的免疫原性和抗原性
  • 批准号:
    10194232
  • 财政年份:
    2021
  • 资助金额:
    $ 41.5万
  • 项目类别:
Ex Vivo Nanoparticle Drug Delivery Targeted to Human Renal Allograft Endothelium
针对人肾同种异体移植物内皮的体外纳米颗粒药物输送
  • 批准号:
    10197784
  • 财政年份:
    2017
  • 资助金额:
    $ 41.5万
  • 项目类别:
Ex Vivo Nanoparticle Drug Delivery Targeted to Human Renal Allograft Endothelium
针对人肾同种异体移植物内皮的体外纳米颗粒药物输送
  • 批准号:
    10155842
  • 财政年份:
    2017
  • 资助金额:
    $ 41.5万
  • 项目类别:
Optimizing Therapeutic Revascularization by Endothelial Cell Transplantation
通过内皮细胞移植优化治疗性血运重建
  • 批准号:
    9516109
  • 财政年份:
    2017
  • 资助金额:
    $ 41.5万
  • 项目类别:
Targeting Nanoparticles for Drug Delivery to Renal Graft Endothelium during Ex Vivo Normothermic Perfusion
体外常温灌注期间靶向纳米颗粒将药物递送至肾移植物内皮
  • 批准号:
    9164300
  • 财政年份:
    2016
  • 资助金额:
    $ 41.5万
  • 项目类别:
Bioengineered siRNA/Nanoparticles to Prevent Human Transplant Rejection
生物工程 siRNA/纳米颗粒可防止人体移植排斥
  • 批准号:
    8693080
  • 财政年份:
    2013
  • 资助金额:
    $ 41.5万
  • 项目类别:
Spatiotemporal Delivery of miRNA Anatgomir for Promoting Vascular Self-Assembly
miRNA Anatgomir 的时空传递促进血管自组装
  • 批准号:
    8322816
  • 财政年份:
    2011
  • 资助金额:
    $ 41.5万
  • 项目类别:
Controlled Spatiotemporal Delivery of miRNA Anatgomir for Promoting Vascular Self
受控时空递送 miRNA Anatgomir 以促进血管自身
  • 批准号:
    8138278
  • 财政年份:
    2011
  • 资助金额:
    $ 41.5万
  • 项目类别:
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