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 autoantibodies before disease onset. The faster C-peptide loss and superior benefits of immunotherapies in individuals with younger-onset type 1 diabetes reinforce the view of age-related endotypes. Clarifying the relative role of T cells will require technical advances in the identification of their target antigens, in their detection and phenotyping in the blood and pancreas, and in the study of the T cell/beta cell crosstalk. Critical steps toward this goal include the understanding of the link with environmental triggers, the description of T cell changes along the natural history of disease, and their relationship with age and the 'benign' islet autoimmunity of healthy individuals. Graphical abstract.
journal_name
Diabetologiajournal_title
Diabetologiaauthors
Carré A,Richardson SJ,Larger E,Mallone Rdoi
10.1007/s00125-020-05298-ysubject
Has Abstractpub_date
2021-01-01 00:00:00pages
15-25issue
1eissn
0012-186Xissn
1432-0428pii
10.1007/s00125-020-05298-yjournal_volume
64pub_type
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