Presumption of guilt for T cells in type 1 diabetes: lead culprits or partners in crime depending on age of onset?

ABSTRACT: Available evidence provides arguments both for and against a primary pathogenic role for T cells in human type 1 diabetes. Genetic susceptibility linked to HLA Class II lends strong support. Histopathology documents HLA Class I hyperexpression and islet infiltrates dominated by CD8⁺ T cells. While both hallmarks are near absent in autoantibody-positive donors, the variable insulitis and residual beta cells of recent-onset donors suggests the existence of a younger-onset endotype with more aggressive autoimmunity and an older-onset endotype with more vulnerable beta cells. Functional arguments from ex vivo and in vitro human studies and in vivo 'humanised' mouse models are instead neutral or against a T cell role. Clinical support is provided by the appearance of islet autoantibo

SUBMITTER: Carre A 

PROVIDER: S-EPMC7717061 | biostudies-literature | 2021 Jan

REPOSITORIES: biostudies-literature