Characterization and Effective Expansion of CD4CD8 TCRαβ T cells from Individuals Living with Type 1 Diabetes

Overview

Journal Mol Ther Methods Clin Dev

Publisher Cell Press

Date 2025 Jan 29

PMID 39877593

Authors

J Ernesto Fajardo-Despaigne

Felix Lombard-Vadnais

Adam-Nicolas Pelletier

Ainhoa Olazabal

Lucie Boutin

Sarah Pasquin

Valerie Janelle

Laurent Legault

Jean-Sebastien Delisle

Erin E Hillhouse

Lise Coderre

Sylvie Lesage

Affiliations

Soon will be listed here.

Abstract

CD4CD8 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 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.

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