Suppression of diabetes by accumulation of non-islet-specific CD8 + effector T cells in pancreatic islets.

Christoffersson G, Chodaczek G, Ratliff SS, Coppieters K, von Herrath MG

Sci Immunol 3 (21) - [2018-03-23; online 2018-03-25]

The inflammatory lesion at the pancreatic islet in type 1 diabetes (T1D) contains a heterogeneous infiltrate of T cells. In human and mouse studies, a large majority (98 to 99%) of the cytotoxic CD8 + T cells (CTLs) within islets are not specific to any islet antigen and are thought to passively add to tissue damage. We show by intravital confocal microscopy the opposite, immune-regulatory function of this cohort of CTLs. Diabetes did not develop in mice with islets showing high levels of infiltration of non-islet-specific CTLs not recognizing local antigens. Accumulation of such CTLs resulted in lower activation and proliferation of islet-specific CTLs, leading them to enter a state of unresponsiveness due to limited access to antigens at the inflammatory lesion. This nonspecific suppression by nonautoreactive CTLs was recapitulated in a model of viral meningitis, may explain viral interference in autoimmunity, and provides insight into the regulation of organ-specific autoimmune responses.

Gustaf Christoffersson

SciLifeLab Fellow

PubMed 29572238

DOI 10.1126/sciimmunol.aam6533

Crossref 10.1126/sciimmunol.aam6533

pii: 3/21/eaam6533

Publications 9.2.2