Slow progressors to type 1 diabetes lose islet autoantibodies over time, have few islet antigen-specific CD8+ T cells and exhibit a distinct CD95hi B cell phenotype

Aims/hypothesis The aim of this study was to characterise islet autoantibody profiles and immune cell phenotypes in slow progressors to type 1 diabetes. Methods Immunological variables were compared across peripheral blood samples obtained from slow progressors to type 1 diabetes, individuals with n...

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Veröffentlicht in:Diabetologia 2020-06, Vol.63 (6), p.1174-1185
Hauptverfasser: Hanna, Stephanie J., Powell, Wendy E., Long, Anna E., Robinson, Emma J. S., Davies, Joanne, Megson, Clare, Howell, Alexandra, Jones, Taz J., Ladell, Kristin, Price, David A., Dayan, Colin M., Williams, Alistair J. K., Gillespie, Kathleen M., Wong, F. Susan
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Sprache:eng
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Zusammenfassung:Aims/hypothesis The aim of this study was to characterise islet autoantibody profiles and immune cell phenotypes in slow progressors to type 1 diabetes. Methods Immunological variables were compared across peripheral blood samples obtained from slow progressors to type 1 diabetes, individuals with newly diagnosed or long-standing type 1 diabetes, and healthy individuals. Polychromatic flow cytometry was used to characterise the phenotypic attributes of B and T cells. Islet autoantigen-specific B cells were quantified using an enzyme-linked immunospot (ELISpot) assay and islet autoantigen-specific CD8 + T cells were quantified using peptide–HLA class I tetramers. Radioimmunoassays were used to detect islet autoantibodies. Sera were assayed for various chemokines, cytokines and soluble receptors via ELISAs. Results Islet autoantibodies were lost over time in slow progressors. Various B cell subsets expressed higher levels of CD95 in slow progressors, especially after polyclonal stimulation, compared with the corresponding B cell subsets in healthy donors ( p  
ISSN:0012-186X
1432-0428
DOI:10.1007/s00125-020-05114-7