Multiplex immune analysis of antigen specific CD4+ T cells in autoimmune diabetes
自身免疫性糖尿病中抗原特异性 CD4 T 细胞的多重免疫分析
基本信息
- 批准号:9271151
- 负责人:
- 金额:$ 40万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2015
- 资助国家:美国
- 起止时间:2015-06-17 至 2020-05-31
- 项目状态:已结题
- 来源:
- 关键词:AffectAllelesAmericanAntigensAutoantibodiesAutoantigensAutoimmune DiabetesBeta CellBiological AssayBiological MarkersCD4 Positive T LymphocytesCell surfaceCellsCessation of lifeChildClinicClinicalClone CellsColorCytometryDevelopmentDiabetes MellitusDiagnosisDiseaseDyesFlow CytometryFrequenciesGenerationsGoalsHeavy MetalsHumanImmuneImmunologic MonitoringImmunologicsIndividualInsulinInsulin-Dependent Diabetes MellitusLabelLeadLifeLife ExpectancyLinkMediatingMethodsMonitoring Clinical TrialsPancreasPathogenesisPatient riskPatientsPeptide/MHC ComplexPeptidesPeripheral Blood Mononuclear CellPhenotypePopulationProductionProinsulinProtocols documentationQuality of lifeReagentResearchRiskSamplingSelf-control as a personality traitSerumStagingStaining methodStainsStreptavidinSystemT-LymphocyteTNFRSF10A geneTechnologyTestingTimeTreatment Efficacyclinical diagnosticsclinical efficacycytokinedisorder riskfluorophoreimmune functioninsulin dependent diabetes mellitus onsetmonomermouse modelnovelnovel markerpreventpublic health relevancerapid detectionscreeningtranscription factortranslational approach
项目摘要
DESCRIPTION (provided by applicant): There is no cure for the 3 million Americans affected by Type 1 diabetes (T1D). Even though daily insulin treatments prolong life expectancy, T1D diminishes the quality of life and leads to life threatening complications. T1D is caused by self-reactive T cell mediated death of insulin producing beta cells. In order to cure T1D, we must remove or control the self-reactive T cells. Until recently, identifying self-reactive T cells has been very difficult. However, recent advances in peptide-MHC tetramer technology and enrichment approaches have allowed us to identify, track and interrogate individual CD4+ T cell clones in both mouse models and humans with T1D. We have generated and validated 2 HLA DQ8 and 3 HLA DR4 diabetes relevant tetramer reagents. The goals of this proposal are to utilize these novel peptide:MHC II tetramer reagents to track and phenotype CD4+ T cell clones involved in human T1D pathogenesis. Currently there are two limitations preventing the successful use of these T1D biomarkers in the clinic. The first problem is that multiple T cell clones cannot be simultaneously analyzed due to limited reagent color combinations. This analysis must be done sequentially for each T cell tetramer. This is further complicated by the fact that individual CD4+ self-reactive clones are exceedingly rare in PBMC samples and must be correctly identified using a double staining protocol using the specific T cell tetramer in two distinct colors. Secondly, we are limited by sample volumes due to the fact that many new onset and patients at risk for developing T1D are children. In this proposal we propose to overcome these two limitations though two distinct but complementary multiplexing assays using CyTOF and flow cytometry. Results from these studies could lead to novel methods for a comprehensive analysis for earlier diabetes diagnosis in humans and novel biomarkers to monitor immune function and therapeutic efficacy in the clinical setting. The rationale for the proposed research is that with a better assay to identify and track multiple self-reactive T cell populations during T1D we will be able to develop translational approaches to selectively eliminate self-destructive T cells to cure autoimmune diabetes.
项目成果
期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
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Brian T Fife其他文献
Brian T Fife的其他文献
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{{ truncateString('Brian T Fife', 18)}}的其他基金
Identifying and preventing antigen specific T cells in diabetes
识别和预防糖尿病中的抗原特异性 T 细胞
- 批准号:
10436364 - 财政年份:2021
- 资助金额:
$ 40万 - 项目类别:
Identifying and preventing antigen specific T cells in diabetes
识别和预防糖尿病中的抗原特异性 T 细胞
- 批准号:
10634700 - 财政年份:2021
- 资助金额:
$ 40万 - 项目类别:
Identifying and preventing antigen specific T cells in diabetes
识别和预防糖尿病中的抗原特异性 T 细胞
- 批准号:
10296946 - 财政年份:2021
- 资助金额:
$ 40万 - 项目类别:
Engineering CAR Tregs for type 1 diabetes
工程 CAR Tregs 治疗 1 型糖尿病
- 批准号:
10495238 - 财政年份:2021
- 资助金额:
$ 40万 - 项目类别:
Engineering CAR Tregs for type 1 diabetes
工程 CAR Tregs 治疗 1 型糖尿病
- 批准号:
10354415 - 财政年份:2021
- 资助金额:
$ 40万 - 项目类别:
Multiplex immune analysis of antigen specific CD4+ T cells in autoimmune diabetes
自身免疫性糖尿病中抗原特异性 CD4 T 细胞的多重免疫分析
- 批准号:
9091431 - 财政年份:2015
- 资助金额:
$ 40万 - 项目类别:
Multiplex immune analysis of antigen specific CD4+ T cells in autoimmune diabetes
自身免疫性糖尿病中抗原特异性 CD4 T 细胞的多重免疫分析
- 批准号:
8932879 - 财政年份:2015
- 资助金额:
$ 40万 - 项目类别:
Mechanisms of immune tolerance in autoimmune diabetes
自身免疫性糖尿病的免疫耐受机制
- 批准号:
8786472 - 财政年份:2013
- 资助金额:
$ 40万 - 项目类别:
Mechanisms of immune tolerance in autoimmune diabetes
自身免疫性糖尿病的免疫耐受机制
- 批准号:
8649238 - 财政年份:2013
- 资助金额:
$ 40万 - 项目类别:
Mechanisms of immune tolerance in autoimmune diabetes
自身免疫性糖尿病的免疫耐受机制
- 批准号:
9181377 - 财政年份:2013
- 资助金额:
$ 40万 - 项目类别:
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