Temporal Alterations in CD8+ T Cells During the Progression from Stage 1 to Stage 3 Type 1 Diabetes
Schroderus, Anna-Mari; Pitkänen, Viola; Ekman, Ilse; Stevens, Daniella; Rytkönen-Nissinen, Marja; Rintamäki, Reeta; Pihlajamäki, Jussi; Knip, Mikael; Veijola, Riitta; Toppari, Jorma; Ilonen, Jorma; Lempainen, Johanna; Kinnunen, Tuure (2024-07-05)
American Diabetes Association
05.07.2024
Anna-Mari Schroderus, Viola Pitkänen, Ilse Ekman, Daniella Stevens, Marja Rytkönen-Nissinen, Reeta Rintamäki, Jussi Pihlajamäki, Mikael Knip, Riitta Veijola, Jorma Toppari, Jorma Ilonen, Johanna Lempainen, Tuure Kinnunen; Temporal Alterations in CD8+ T Cells During the Progression From Stage 1 to Stage 3 Type 1 Diabetes. Diabetes 20 September 2024; 73 (10): 1705–1715. https://doi.org/10.2337/db24-0159
https://rightsstatements.org/vocab/InC/1.0/
© 2024 by the American Diabetes Association. This is an author-created, uncopyedited electronic version of an article accepted for publication in Diabetes. The American Diabetes Association (ADA), publisher of Diabetes, is not responsible for any errors or omissions in this version of the manuscript or any version derived from it by third parties. The definitive publisher-authenticated version will be available in a future issue of Diabetes in print and online at https://diabetesjournals.org/diabetes/article-abstract/73/10/1705/156950.
https://rightsstatements.org/vocab/InC/1.0/
© 2024 by the American Diabetes Association. This is an author-created, uncopyedited electronic version of an article accepted for publication in Diabetes. The American Diabetes Association (ADA), publisher of Diabetes, is not responsible for any errors or omissions in this version of the manuscript or any version derived from it by third parties. The definitive publisher-authenticated version will be available in a future issue of Diabetes in print and online at https://diabetesjournals.org/diabetes/article-abstract/73/10/1705/156950.
https://rightsstatements.org/vocab/InC/1.0/
Julkaisun pysyvä osoite on
https://urn.fi/URN:NBN:fi:oulu-202504252909
https://urn.fi/URN:NBN:fi:oulu-202504252909
Tiivistelmä
Abstract
CD8+ T cells are perceived to play a major role in the pathogenesis of type 1 diabetes (T1D). In this study, we characterized the function and phenotype of circulating CD8+ memory T cells in samples from individuals at different stages of T1D progression using flow cytometry and single-cell multiomics. We observed two distinct CD8+ T-cell signatures during progression of T1D within the highly differentiated CD27−CD8+ memory T-cell subset. A proinflammatory signature, with an increased frequency of IFN-γ+TNF-α+ CD27−CD8+ memory T cells, was observed in children with newly diagnosed T1D (stage 3) and correlated with the level of dysglycemia at diagnosis. In contrast, a coinhibitory signature, with an increased frequency of KLRG1+TIGIT+ CD27−CD8+ memory T cells, was observed in islet autoantibody-positive children who later progressed to T1D (stage 1). No alterations within CD27−CD8+ memory T cells were observed in adults with established T1D or in children during the initial seroconversion to islet autoantibody positivity. Single-cell multiomics analyses suggested that CD27−CD8+ T cells expressing the IFNG+TNF+ proinflammatory signature may be distinct from those expressing the KLRG1+TIGIT+ coinhibitory signature at the single-cell level. Collectively, our findings suggest that distinct blood CD8+ T-cell signatures could be employed as potential biomarkers of T1D progression.
CD8+ T cells are perceived to play a major role in the pathogenesis of type 1 diabetes (T1D). In this study, we characterized the function and phenotype of circulating CD8+ memory T cells in samples from individuals at different stages of T1D progression using flow cytometry and single-cell multiomics. We observed two distinct CD8+ T-cell signatures during progression of T1D within the highly differentiated CD27−CD8+ memory T-cell subset. A proinflammatory signature, with an increased frequency of IFN-γ+TNF-α+ CD27−CD8+ memory T cells, was observed in children with newly diagnosed T1D (stage 3) and correlated with the level of dysglycemia at diagnosis. In contrast, a coinhibitory signature, with an increased frequency of KLRG1+TIGIT+ CD27−CD8+ memory T cells, was observed in islet autoantibody-positive children who later progressed to T1D (stage 1). No alterations within CD27−CD8+ memory T cells were observed in adults with established T1D or in children during the initial seroconversion to islet autoantibody positivity. Single-cell multiomics analyses suggested that CD27−CD8+ T cells expressing the IFNG+TNF+ proinflammatory signature may be distinct from those expressing the KLRG1+TIGIT+ coinhibitory signature at the single-cell level. Collectively, our findings suggest that distinct blood CD8+ T-cell signatures could be employed as potential biomarkers of T1D progression.
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