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Sci Immunol. 2018 Mar 23;3(21). pii: eaam6533. doi: 10.1126/sciimmunol.aam6533.

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

Author information

1
Type 1 Diabetes Center, La Jolla Institute for Allergy and Immunology, La Jolla, CA 92037, USA.
2
Wroclaw Research Centre EIT+, Wroclaw, Poland.
3
Novo Nordisk Diabetes Research and Development Center, Seattle, WA 98109, USA.
4
Type 1 Diabetes Center, La Jolla Institute for Allergy and Immunology, La Jolla, CA 92037, USA. matthias@lji.org.

Abstract

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.

PMID:
29572238
DOI:
10.1126/sciimmunol.aam6533
[Indexed for MEDLINE]

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