Demonstration of Tissue Resident Memory CD8 T Cells in Insulitic Lesions in Adult Patients with Recent-Onset Type 1 Diabetes
| Autor: | Trond Buanes, Enida Kuric, Lars Krogvold, Knut Dahl-Jørgensen, Peter Seiron, Kristian F. Hanssen, Bjørn Edwin, Olle Korsgren, Oskar Skog |
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| Jazyk: | angličtina |
| Rok vydání: | 2017 |
| Předmět: |
Adult
Male 0301 basic medicine Pathology medicine.medical_specialty CD3 Autoimmunity 030209 endocrinology & metabolism Inflammation CD8-Positive T-Lymphocytes Endocrinology and Diabetes medicine.disease_cause Pathology and Forensic Medicine 03 medical and health sciences 0302 clinical medicine Biopsy medicine Humans Insulin Cytotoxic T cell medicine.diagnostic_test biology medicine.disease 3. Good health Diabetes Mellitus Type 1 030104 developmental biology medicine.anatomical_structure Gene Expression Regulation Immunology Endokrinologi och diabetes biology.protein Female medicine.symptom Immunologic Memory Memory T cell Insulitis CD8 |
| Popis: | 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 (T RM ) (CD8 + CD69 + CD103 + ) phenotype in T1D subjects. Most T RM cells were located in the insulitic lesion in the endocrine-exocrine interface. T RM 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 T RM 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. |
| Databáze: | OpenAIRE |
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