Characterization and effective expansion of CD4^-CD8^- TCRαβ⁺ T cells from individuals living with type 1 diabetes.

IF 4.6 2区医学 Q2 MEDICINE, RESEARCH & EXPERIMENTAL

Molecular Therapy-Methods & Clinical Development Pub Date : 2024-12-17 eCollection Date: 2025-03-13 DOI:10.1016/j.omtm.2024.101400

J Ernesto Fajardo-Despaigne, Félix Lombard-Vadnais, Adam-Nicolas Pelletier, Aïnhoa Olazabal, Lucie Boutin, Sarah Pasquin, Valérie Janelle, Laurent Legault, Jean-Sébastien Delisle, Erin E Hillhouse, Lise Coderre, Sylvie Lesage

{"title":"Characterization and effective expansion of CD4-CD8- TCRαβ+ T cells from individuals living with type 1 diabetes.","authors":"J Ernesto Fajardo-Despaigne, Félix Lombard-Vadnais, Adam-Nicolas Pelletier, Aïnhoa Olazabal, Lucie Boutin, Sarah Pasquin, Valérie Janelle, Laurent Legault, Jean-Sébastien Delisle, Erin E Hillhouse, Lise Coderre, Sylvie Lesage","doi":"10.1016/j.omtm.2024.101400","DOIUrl":null,"url":null,"abstract":"CD4-CD8- TCRαβ+ (double-negative [DN]) T cells represent a rare T cell population that promotes immunological tolerance through various cytotoxic mechanisms. In mice, autologous transfer of DN T cells has shown protective effects against autoimmune diabetes and graft-versus-host disease. Here, we characterized human DN T cells from people living with type 1 diabetes (PWT1D) and healthy controls. We found that while DN T cells and CD8+ T cells share many similarities, DN T cells are a unique T cell population, both at the transcriptomic and protein levels. We also show that by using various cytokine combinations, human DN T cells can be expanded in vitro up to 1,000-fold (mean >250-fold) and remain functional post-expansion. In addition, we report that DN T cells from PWT1D display a phenotype comparable to that of healthy controls, efficiently expand, and are highly functional. As DN T cells are immunoregulatory and can prevent T1D in various mouse models, these observations suggest that autologous DN T cells may be amenable to therapy for the prevention or treatment of T1D.","PeriodicalId":54333,"journal":{"name":"Molecular Therapy-Methods & Clinical Development","volume":"33 1","pages":"101400"},"PeriodicalIF":4.6000,"publicationDate":"2024-12-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11772147/pdf/","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Molecular Therapy-Methods & Clinical Development","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1016/j.omtm.2024.101400","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2025/3/13 0:00:00","PubModel":"eCollection","JCR":"Q2","JCRName":"MEDICINE, RESEARCH & EXPERIMENTAL","Score":null,"Total":0}

引用次数: 0

Abstract

CD4^-CD8^- TCRαβ⁺ (double-negative [DN]) T cells represent a rare T cell population that promotes immunological tolerance through various cytotoxic mechanisms. In mice, autologous transfer of DN T cells has shown protective effects against autoimmune diabetes and graft-versus-host disease. Here, we characterized human DN T cells from people living with type 1 diabetes (PWT1D) and healthy controls. We found that while DN T cells and CD8⁺ T cells share many similarities, DN T cells are a unique T cell population, both at the transcriptomic and protein levels. We also show that by using various cytokine combinations, human DN T cells can be expanded in vitro up to 1,000-fold (mean >250-fold) and remain functional post-expansion. In addition, we report that DN T cells from PWT1D display a phenotype comparable to that of healthy controls, efficiently expand, and are highly functional. As DN T cells are immunoregulatory and can prevent T1D in various mouse models, these observations suggest that autologous DN T cells may be amenable to therapy for the prevention or treatment of T1D.

查看原文本刊更多论文

求助全文

约1分钟内获得全文求助全文

来源期刊

Molecular Therapy-Methods & Clinical Development Biochemistry, Genetics and Molecular Biology-Molecular Biology

CiteScore

9.90

自引率

4.30%

发文量

163

审稿时长

12 weeks

期刊介绍： The aim of Molecular Therapy—Methods & Clinical Development is to build upon the success of Molecular Therapy in publishing important peer-reviewed methods and procedures, as well as translational advances in the broad array of fields under the molecular therapy umbrella. Topics of particular interest within the journal''s scope include: Gene vector engineering and production, Methods for targeted genome editing and engineering, Methods and technology development for cell reprogramming and directed differentiation of pluripotent cells, Methods for gene and cell vector delivery, Development of biomaterials and nanoparticles for applications in gene and cell therapy and regenerative medicine, Analysis of gene and cell vector biodistribution and tracking, Pharmacology/toxicology studies of new and next-generation vectors, Methods for cell isolation, engineering, culture, expansion, and transplantation, Cell processing, storage, and banking for therapeutic application, Preclinical and QC/QA assay development, Translational and clinical scale-up and Good Manufacturing procedures and process development, Clinical protocol development, Computational and bioinformatic methods for analysis, modeling, or visualization of biological data, Negotiating the regulatory approval process and obtaining such approval for clinical trials.