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Rodriguez-Calvo, T. ; Christoffersson, G.* ; Bender, C.* ; Von Herrath, M.G.* ; Mallone, R.* ; Kent, S.C.* ; James, E.A.*

Means, motive, and opportunity: Do non-islet-reactive infiltrating T cells contribute to autoimmunity in type 1 diabetes?

Front. Immunol. 12:683091 (2021)
Verlagsversion DOI PMC
Open Access Gold
Creative Commons Lizenzvertrag
In human type 1 diabetes and animal models of the disease, a diverse assortment of immune cells infiltrates the pancreatic islets. CD8+ T cells are well represented within infiltrates and HLA multimer staining of pancreas sections provides clear evidence that islet epitope reactive T cells are present within autoimmune lesions. These bona fide effectors have been a key research focus because these cells represent an intellectually attractive culprit for β cell destruction. However, T cell receptors are highly diverse in human insulitis. This suggests correspondingly broad antigen specificity, which includes a majority of T cells for which there is no evidence of islet-specific reactivity. The presence of "non-cognate" T cells in insulitis raises suspicion that their role could be beyond that of an innocent bystander. In this perspective, we consider the potential pathogenic contribution of non-islet-reactive T cells. Our intellectual framework will be that of a criminal investigation. Having arraigned islet-specific CD8+ T cells for the murder of pancreatic β cells, we then turn our attention to the non-target immune cells present in human insulitis and consider the possible regulatory, benign, or effector roles that they may play in disease. Considering available evidence, we overview the case that can be made that non-islet-reactive infiltrating T cells should be suspected as co-conspirators or accessories to the crime and suggest some possible routes forward for reaching a better understanding of their role in disease.
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Publikationstyp Artikel: Journalartikel
Dokumenttyp Review
Korrespondenzautor
Schlagwörter Autoreactive T Cells ; Insulitis ; Non-islet Reactive T Cells ; Type 1 Diabetes ; β Cell Destruction; Beta-cell; Multiple-sclerosis; Interferon-gamma; Recent-onset; Insulitis; Expression; Inflammation; Pancreas; Self; Mass
ISSN (print) / ISBN 1664-3224
e-ISSN 1664-3224
Zeitschrift Frontiers in Immunology
Quellenangaben Band: 12, Heft: , Seiten: , Artikelnummer: 683091 Supplement: ,
Verlag Frontiers
Verlagsort Avenue Du Tribunal Federal 34, Lausanne, Ch-1015, Switzerland
Nichtpatentliteratur Publikationen
Begutachtungsstatus Peer reviewed
Institut(e) Institute of Diabetes Research Type 1 (IDF)
Förderungen National Institute of Diabetes and Digestive and Kidney Diseases
Swedish Society for Medical Research
Goran Gustafsson Foundation
Science for Life Laboratory
National Institute of Diabetes and Digestive and Kidney Diseases (Human Islet Research Network)
Fondation pour la Recherche Medicale
Agence Nationale de la Recherche
Innovative Medicines Initiative 2 Joint Undertaking
Union's Horizon 2020 research and innovation programme
European Federation of Pharmaceutical Industries Associations
JDRF
Leona M. and Harry B. Helmsley Charitable Trust
NIH
Swedish Research Council