Characterization and effective expansion of CD4−CD8− TCRαβ+ T cells from individuals living with type 1 diabetes
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 ch...
Saved in:
| Main Authors: | , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2025-03-01
|
| Series: | Molecular Therapy: Methods & Clinical Development |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S232905012400216X |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1841545514863034368 |
|---|---|
| author | 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 |
| author_facet | 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 |
| author_sort | J. Ernesto Fajardo-Despaigne |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-7b5a439ce6dd4946b8b4fd77d621c514 |
| institution | Kabale University |
| issn | 2329-0501 |
| language | English |
| publishDate | 2025-03-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Molecular Therapy: Methods & Clinical Development |
| spelling | doaj-art-7b5a439ce6dd4946b8b4fd77d621c5142025-01-12T05:25:14ZengElsevierMolecular Therapy: Methods & Clinical Development2329-05012025-03-01331101400Characterization and effective expansion of CD4−CD8− TCRαβ+ T cells from individuals living with type 1 diabetesJ. Ernesto Fajardo-Despaigne0Félix Lombard-Vadnais1Adam-Nicolas Pelletier2Aïnhoa Olazabal3Lucie Boutin4Sarah Pasquin5Valérie Janelle6Laurent Legault7Jean-Sébastien Delisle8Erin E. Hillhouse9Lise Coderre10Sylvie Lesage11Immunologie-Oncologie, Centre de Recherche de l’Hôpital Maisonneuve-Rosemont, Montréal, QC, CanadaImmunologie-Oncologie, Centre de Recherche de l’Hôpital Maisonneuve-Rosemont, Montréal, QC, CanadaRPM Bioinfo Solutions, Sainte-Thérèse, QC, CanadaImmunologie-Oncologie, Centre de Recherche de l’Hôpital Maisonneuve-Rosemont, Montréal, QC, Canada; Département de Microbiologie, Infectiologie et Immunologie, Université de Montréal, Montréal, QC, CanadaDépartement de Recherche Clinique, CIUSSS de l’Est-de-l’Île-de-Montréal, Montréal, QC, CanadaImmunologie-Oncologie, Centre de Recherche de l’Hôpital Maisonneuve-Rosemont, Montréal, QC, Canada; Département de Microbiologie, Infectiologie et Immunologie, Université de Montréal, Montréal, QC, CanadaImmunologie-Oncologie, Centre de Recherche de l’Hôpital Maisonneuve-Rosemont, Montréal, QC, CanadaDépartement de Recherche Clinique, CIUSSS de l’Est-de-l’Île-de-Montréal, Montréal, QC, Canada; Department of Pediatrics, Montreal Children’s Hospital, Montreal, QC, CanadaImmunologie-Oncologie, Centre de Recherche de l’Hôpital Maisonneuve-Rosemont, Montréal, QC, Canada; Département de Médecine, Université de Montréal, Montréal, QC, CanadaImmunologie-Oncologie, Centre de Recherche de l’Hôpital Maisonneuve-Rosemont, Montréal, QC, Canada; Département de Microbiologie, Infectiologie et Immunologie, Université de Montréal, Montréal, QC, CanadaImmunologie-Oncologie, Centre de Recherche de l’Hôpital Maisonneuve-Rosemont, Montréal, QC, Canada; Département de Microbiologie, Infectiologie et Immunologie, Université de Montréal, Montréal, QC, CanadaImmunologie-Oncologie, Centre de Recherche de l’Hôpital Maisonneuve-Rosemont, Montréal, QC, Canada; Département de Microbiologie, Infectiologie et Immunologie, Université de Montréal, Montréal, QC, Canada; Corresponding author: Sylvie Lesage, Immunologie-Oncologie, Centre de Recherche de l’Hôpital Maisonneuve-Rosemont, Montréal, QC, Canada.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.http://www.sciencedirect.com/science/article/pii/S232905012400216XDN T cellsunconventional T cellcell therapytype 1 diabetescellular expansiontolerance |
| spellingShingle | 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 Characterization and effective expansion of CD4−CD8− TCRαβ+ T cells from individuals living with type 1 diabetes Molecular Therapy: Methods & Clinical Development DN T cells unconventional T cell cell therapy type 1 diabetes cellular expansion tolerance |
| title | Characterization and effective expansion of CD4−CD8− TCRαβ+ T cells from individuals living with type 1 diabetes |
| title_full | Characterization and effective expansion of CD4−CD8− TCRαβ+ T cells from individuals living with type 1 diabetes |
| title_fullStr | Characterization and effective expansion of CD4−CD8− TCRαβ+ T cells from individuals living with type 1 diabetes |
| title_full_unstemmed | Characterization and effective expansion of CD4−CD8− TCRαβ+ T cells from individuals living with type 1 diabetes |
| title_short | Characterization and effective expansion of CD4−CD8− TCRαβ+ T cells from individuals living with type 1 diabetes |
| title_sort | characterization and effective expansion of cd4 cd8 tcrαβ t cells from individuals living with type 1 diabetes |
| topic | DN T cells unconventional T cell cell therapy type 1 diabetes cellular expansion tolerance |
| url | http://www.sciencedirect.com/science/article/pii/S232905012400216X |
| work_keys_str_mv | AT jernestofajardodespaigne characterizationandeffectiveexpansionofcd4cd8tcrabtcellsfromindividualslivingwithtype1diabetes AT felixlombardvadnais characterizationandeffectiveexpansionofcd4cd8tcrabtcellsfromindividualslivingwithtype1diabetes AT adamnicolaspelletier characterizationandeffectiveexpansionofcd4cd8tcrabtcellsfromindividualslivingwithtype1diabetes AT ainhoaolazabal characterizationandeffectiveexpansionofcd4cd8tcrabtcellsfromindividualslivingwithtype1diabetes AT lucieboutin characterizationandeffectiveexpansionofcd4cd8tcrabtcellsfromindividualslivingwithtype1diabetes AT sarahpasquin characterizationandeffectiveexpansionofcd4cd8tcrabtcellsfromindividualslivingwithtype1diabetes AT valeriejanelle characterizationandeffectiveexpansionofcd4cd8tcrabtcellsfromindividualslivingwithtype1diabetes AT laurentlegault characterizationandeffectiveexpansionofcd4cd8tcrabtcellsfromindividualslivingwithtype1diabetes AT jeansebastiendelisle characterizationandeffectiveexpansionofcd4cd8tcrabtcellsfromindividualslivingwithtype1diabetes AT erinehillhouse characterizationandeffectiveexpansionofcd4cd8tcrabtcellsfromindividualslivingwithtype1diabetes AT lisecoderre characterizationandeffectiveexpansionofcd4cd8tcrabtcellsfromindividualslivingwithtype1diabetes AT sylvielesage characterizationandeffectiveexpansionofcd4cd8tcrabtcellsfromindividualslivingwithtype1diabetes |