T cells accumulate in non-diabetic islets during ageing

Abstract

Background The resident immune population of pancreatic islets has roles in islet development, beta cell physiology, and the pathology of diabetes. These roles have largely been attributed to islet macrophages, comprising 90% of islet immune cells (in the absence of islet autoimmunity), and, in the case of type 1 diabetes, to infiltrating autoreactive T cells. In adipose, tissue-resident and recruited T and B cells have been implicated in the development of insulin resistance during diet-induced obesity and ageing, but whether this is paralleled in the pancreatic islets is not known. Here, we investigated the non-macrophage component of resident islet immune cells in islets isolated from C57BL/6 J male mice during ageing (3 to 24 months of age) and following similar weight gain achieved by 12 weeks of 60% high fat diet. Immune cells were also examined by flow cytometry in cadaveric non-diabetic human islets. Results Immune cells comprised 2.7 ± 1.3% of total islet cells in non-diabetic mouse islets, and 2.3 ± 1.7% of total islet cells in non-diabetic human islets. In 3-month old mice on standard diet, B and T cells each comprised approximately 2–4% of the total islet immune cell compartment, and approximately 0.1% of total islet cells. A similar amount of T cells were present in non-diabetic human islets. The majority of islet T cells expressed the αβ T cell receptor, and were comprised of CD8-positive, CD4-positive, and regulatory T cells, with a minor population of γδ T cells. Interestingly, the number of islet T cells increased linearly (R2 = 0.9902) with age from 0.10 ± 0.05% (3 months) to 0.38 ± 0.11% (24 months) of islet cells. This increase was uncoupled from body weight, and was not phenocopied by a degree similar weight gain induced by high fat diet in mice. Conclusions This study reveals that T cells are a part of the normal islet immune population in mouse and human islets, and accumulate in islets during ageing in a body weight-independent manner. Though comprising only a small subset of the immune cells within islets, islet T cells may play a role in the physiology of islet ageing.

IL-1beta promotes the age-associated decline of beta cell function

“…iScience Article possible that IL-1beta indirectly impairs beta cells through IL-1beta-induced chemokines and age-associated increase of T cells (Denroche et al, 2021).…”

Interactions between islets and regulatory immune cells in health and type 1 diabetes

“…Mϕs constitute the majority of leucocytes detected in the islets of non-diabetic humans [39] and NOD mice before the onset of inflammation [40]. In NOD mice, Mϕs are in close contact with beta cells, sampling and presenting the contents of islet secretory granules, such as insulin peptides, to T cells [41].…”

Islet Lymphocytes Maintain a Stable Regulatory Phenotype Under Homeostatic Conditions and Metabolic Stress

“…In addition to macrophages, T cells and B cells have been identified in non-diabetic human and mouse islets ( 14 – 18 ). In human islets, 80% of the T cells were memory CD8 T cells, with most of the cells also expressing CD103 ( 14 ).…”

“…In human islets, 80% of the T cells were memory CD8 T cells, with most of the cells also expressing CD103 ( 14 ). In murine islets, the T cell compartment includes CD4+, CD8+ and regulatory T cells which increase with age ( 18 ). B cells have also been identified in human and mouse islets at low numbers ( 14 – 18 ).…”

“…In murine islets, the T cell compartment includes CD4+, CD8+ and regulatory T cells which increase with age ( 18 ). B cells have also been identified in human and mouse islets at low numbers ( 14 – 18 ). It is unclear what function islet T cells and B cells may be performing and how these populations change when the islet environment is altered by inflammation.…”