Islet transplantation in autoimmune diabetes
Islet transplantation in autoimmune diabetes
批准号:
8697580
负责人:
Ronald G Gill
金额:
$30.34万
依托单位国家:
美国
项目类别:
财政年份:
2014
资助国家:
美国
项目状态:
已结题
起止时间:
2014-07-01 至 2017-06-30
关键词:
AddressAlloantigenAllogenicAllograft ToleranceAllograftingAnimalsAntigensAutoantigensAutoimmune DiabetesAutoimmune ProcessAutoimmunityCD4 Positive T LymphocytesCD8B1 geneCellsCellular StructuresClinicalDevelopmentDiseaseFailureFoundationsFutureGeneticGlareGoalsGraft RejectionImmuneImmunityInbred NOD MiceInfectionInflammationInsulinInterventionIslets of Langerhans TransplantationIsogenic transplantationKnowledgeLeadMHC Class I GenesMediatingMemoryMemory B-LymphocyteNatureNon obeseOrgan TransplantationPathogenesisPathologyPathway interactionsPopulationPre-Clinical ModelRecurrenceRefractoryRelative (related person)ResistanceRoleSourceSpecificityT memory cellT-Cell Immunologic SpecificityT-LymphocyteTestingTherapeuticTimeTissuesTransplantationTransplantation Toleranceallograft rejectionautoreactive T cellautoreactivitycombatcross reactivitydesigndiabeticeffective therapyexperienceinjuredisletislet allograftnovelpathogenpre-clinicalpublic health relevanceresponsesuccesstreatment strategytype I diabetic
中文摘要
描述(由申请人提供):尽管关于同种异体T细胞与自身反应性T细胞在胰岛移植破坏中的相对贡献的争论已经超过二十年
英文摘要
DESCRIPTION (provided by applicant): Despite debate for more than two decades on the relative contribution of alloreactive versus autoreactive T cells in islet allograft destruction in
autoimmune Type 1 diabetic (T1D) recipients, there has been a surprising paucity of basic studies that directly interrogate the types and specificities of T cells that actually infiltrate ad injure islet grafts in the autoimmune setting. This issue itself constitutes a glaring gap in curret information regarding the pathogenesis of islet transplant rejection in autoimmune recipients. Therefore, the general goal of this project is to determine the nature of T cells responsible for islet allograft destruction in the non-obese diabetic (NOD) pre-clinical model of T1D. Moreover, while it is clear that NOD mice are resistant to allograft tolerance, it is not at all clear what tpes of T cells are actually responsible for such tolerance-resistant graft rejection. Many previous studies have highlighted the role of memory T cells, inflammation, pathogen infection, and genetic resistance as general barriers to transplantation tolerance induction. This proposal sets out to explore the nature of spontaneous autoimmunity as another related endogenous barrier to allograft tolerance. That is, this project will also determine the nature of T cells (autoreactie and/or alloreactive) responsible for islet allograft recognition and, importantly, thos that resist
tolerance-promoting therapies NOD mice. These general goals will be addressed through the following Specific Aims: Specific Aim 1: Determine primary T cell recognition pathway(s) that distinguish between the destruction of syngeneic versus allogeneic islet transplants in autoimmune NOD mice. This initial aim will test the hypothesis that CD4 T cells with autoimmune (islet-reactive) specificity comprise the primary component of cells targeting even MHC-unrelated islet allografts. This aim will attempt to either support or refute this primary hypothesis. Specific Aim 2: Determine the actual antigen specificity and T cells targeting islet transplants in NOD mice. This aim will attempt to support or refute the hypothesis that dual auto-/allo-reactive 'heterologous' T cells are specifically enriched in islet allografts. Specific im 3: Determine the nature of T cells responsible for 'tolerance resistant' islet allograft rejection n NOD mice. This Aim addresses the practical/translational issue of determining the nature of T cell reactivity that is refractory to tolerance-promoting therapies in the setting of autoimmune diabetes. There is a pressing need to develop novel and effective therapies to promote islet allograft survival in diabetic recipients. However, we believe that results from this project form primary and essential foundation for guiding such therapeutic design by clarifying the actual types of T cells that form key rate-limiting barriers to current treatment strategies.
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Tolerance Blockade by Immune Memory
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批准号:10207614
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项目类别:
-
资助金额:$38.88万
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财政年份:2018
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负责人:Ronald G Gill
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依托单位:
CORE--BIORESOURCES
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批准号:7858102
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项目类别:
-
资助金额:$23.49万
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财政年份:2009
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负责人:Ronald G Gill
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依托单位:
CORE--BIORESOURCES
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批准号:7311611
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项目类别:
-
资助金额:$22.69万
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财政年份:2006
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负责人:Ronald G Gill
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依托单位:
ISLET CELL RESOURCES TYPE1 DIABETES: TRANSPLANTATION: CYSTIC FIBROSIS
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批准号:7167013
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项目类别:
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资助金额:$99.93万
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财政年份:2005
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负责人:Ronald G Gill
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依托单位:
ISLET CELL RESOURCES TYPE1 DIABETES: TRANSPLANTATION: CYSTIC FIBROSIS
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批准号:6982949
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项目类别:
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资助金额:$3.99万
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财政年份:2004
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负责人:Ronald G Gill
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依托单位:
Correcting dysregulated peripheral tolerance in NOD mice
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批准号:6730228
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项目类别:
-
资助金额:$22.98万
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财政年份:2003
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负责人:Ronald G Gill
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依托单位:
Correcting dysregulated peripheral tolerance in NOD mice
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批准号:6806459
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项目类别:
-
资助金额:$22.98万
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财政年份:2003
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负责人:Ronald G Gill
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依托单位:
ISLET CELL RESOURCES (ICR) FAC AT THE UNIVERSITY OF *
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批准号:7038453
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项目类别:
-
资助金额:$33.61万
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财政年份:2001
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负责人:Ronald G Gill
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依托单位:
ISLET CELL RESOURCES (ICR) FAC AT THE UNIVERSITY OF *
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批准号:6951912
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项目类别:
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资助金额:$66.32万
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财政年份:2001
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负责人:Ronald G Gill
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依托单位:
ISLET CELL RESOURCES (ICR) FAC AT THE UNIVERSITY OF *
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批准号:6802335
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项目类别:
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资助金额:$3.99万
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财政年份:2001
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负责人:Ronald G Gill
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依托单位:
CORE--ANIMAL FACILITY
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批准号:6444621
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项目类别:
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资助金额:$25.0万
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财政年份:2001
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负责人:Ronald G Gill
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依托单位:
ISLET CELL RESOURCES (ICR) FAC AT THE UNIVERSITY OF *
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批准号:6439975
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项目类别:
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资助金额:$75.5万
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财政年份:2001
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负责人:Ronald G Gill
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依托单位:
ISLET CELL RESOURCES (ICR) FAC AT THE UNIVERSITY OF *
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批准号:6668636
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项目类别:
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资助金额:$20.0万
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财政年份:2001
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负责人:Ronald G Gill
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依托单位:
GENERATING OF ALLOREACTIVE CD4+T TRANSGENIC MICE
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批准号:6498205
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项目类别:
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资助金额:$15.1万
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财政年份:2001
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负责人:Ronald G Gill
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依托单位:
ISLET CELL RESOURCES (ICR) FAC AT THE UNIVERSITY OF *
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批准号:6530174
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项目类别:
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资助金额:$48.16万
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财政年份:2001
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负责人:Ronald G Gill
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依托单位:
GENERATING OF ALLOREACTIVE CD4+T TRANSGENIC MICE
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批准号:6258102
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项目类别:
-
资助金额:$15.1万
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财政年份:2001
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负责人:Ronald G Gill
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依托单位:
CORE--ANIMAL FACILITY
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批准号:6331775
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项目类别:
-
资助金额:$25.0万
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财政年份:2000
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负责人:Ronald G Gill
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依托单位:
T CELL MEDIATED INJURY TO ISLET ALLOGRAFTS
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批准号:6177403
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项目类别:
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资助金额:$21.68万
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财政年份:1998
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负责人:Ronald G Gill
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依托单位:
T cell mediated injury to islet allografts
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批准号:6400674
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项目类别:
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资助金额:$26.43万
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财政年份:1998
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负责人:Ronald G Gill
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依托单位:
T cell mediated injury to islet allografts
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批准号:6649752
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项目类别:
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资助金额:$26.43万
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财政年份:1998
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负责人:Ronald G Gill
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依托单位:
海外基金