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Am J Pathol. 2017 Mar;187(3):581-588. doi: 10.1016/j.ajpath.2016.11.002.

Demonstration of Tissue Resident Memory CD8 T Cells in Insulitic Lesions in Adult Patients with Recent-Onset Type 1 Diabetes.

Author information

1
Department of Immunology, Genetics and Pathology, Uppsala University, Uppsala, Sweden. Electronic address: enida.kuric@igp.uu.se.
2
Department of Immunology, Genetics and Pathology, Uppsala University, Uppsala, Sweden.
3
Division of Paediatric and Adolescent Medicine, Oslo University Hospital, Oslo, Norway; Faculty of Medicine, University of Oslo, Oslo, Norway.
4
Faculty of Medicine, University of Oslo, Oslo, Norway; Department of Surgery, The Intervention Centre, Oslo University Hospital, Oslo, Norway; Department of Pathology, Oslo University Hospital, Oslo, Norway.
5
Faculty of Medicine, University of Oslo, Oslo, Norway; Division of Cancer, Surgery and Transplantation, Oslo University Hospital, Oslo, Norway.
6
Faculty of Medicine, University of Oslo, Oslo, Norway; Department of Endocrinology, Oslo University Hospital, Oslo, Norway.

Abstract

Subtypes of CD8+ T cells in insulitic lesions in biopsy specimens from six subjects with recent-onset type 1 diabetes (T1D) and six nondiabetic matched controls were analyzed using simultaneous multicolor immunofluorescence. Also, insulitic islets based on accumulation of CD3+ T cells were microdissected with laser-capture microscopy, and gene transcripts associated with inflammation and autoimmunity were analyzed. We found a substantial proportion, 43%, of the CD8+ T cells in the insulitic lesions to display a tissue resident memory T cell (TRM) (CD8+CD69+CD103+) phenotype in T1D subjects. Most TRM cells were located in the insulitic lesion in the endocrine-exocrine interface. TRM cells were also sporadically found in islets of control subjects. Moreover, gene expression analysis showed a lack of active transcription of genes associated with acute inflammatory or cytotoxic T-cell responses. We present evidence that a substantial proportion of T cells in insulitic lesions of recent-onset T1D patients are TRM cells and not classic cytotoxic CD8+ T cells. Our findings highlight the need for further analysis of the T cells involved in insulitis to elucidate their role in the etiology of T1D.

PMID:
28212742
DOI:
10.1016/j.ajpath.2016.11.002
[Indexed for MEDLINE]

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