T cells are present in non-diabetic islets and accumulate during aging.

Abstract

BackgroundThe 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 aging, 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/6J male mice during aging (3 to 24 months of age) and following diet-induced obesity (12 weeks 60% high fat diet). Immune cells were also examined by flow cytometry in cadaveric non-diabetic human islets. ResultsImmune 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. Islet T cells were comprised of CD8-positive, CD4-positive, and regulatory T cells. Interestingly, while islet B cells and macrophage numbers were unaltered by age, 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. ConclusionsThis study reveals that T cells are a part of the normal islet immune population in mouse and human islets, and that they accumulate in islets during aging 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 aging.