Abstract
Aims/hypothesisPancreatic lymph nodes (PLNs) are critical sites for the initial interaction between islet autoantigens and autoreactive lymphocytes, but the histology of PLNs in tissue from individuals with type 1 diabetes has not been analysed in detail. The aim of this study was to examine PLN tissue sections from healthy donors compared with those at risk of, or with recent-onset and longer-duration type 1 diabetes.MethodsImmunofluorescence staining was used to examine PLN sections from the following donor groups: non-diabetic (n=15), non-diabetic islet autoantibody-positive (n=5), recent-onset (≤1.5 years duration) type 1 diabetes (n=13), and longer-duration type 1 diabetes (n=15). Staining for CD3, CD20 and Ki67 was used to detect primary and secondary (germinal centre-containing) follicles and CD21 and CD35 to detect follicular dendritic cell networks.ResultsThe frequency of secondary follicles was lower in the recent-onset type 1 diabetes group compared with the non-diabetic control group. The presence of insulitis (as evidence of ongoing beta cell destruction) and diagnosis of type 1 diabetes at a younger age, however, did not appear to be associated with a lower frequency of secondary follicles. A higher proportion of primary B cell follicles were observed to lack follicular dendritic cell networks in the recent-onset type 1 diabetes group.Conclusions/interpretationHistological analysis of rare PLNs from individuals with type 1 diabetes suggests a previously unrecognised phenotype comprising decreased primary B cell follicle frequency and fewer follicular dendritic cell networks in recent-onset type 1 diabetes.
Highlights
Type 1 diabetes develops as a result of the immune-mediated destruction of insulin-secreting beta cells in the islets of Langerhans of the pancreas
Evidence of insulitis has been reported in histological pancreas specimens from donors with recent-onset type 1 diabetes, along with a marked reduction in islets that stain positively for insulin compared with specimens from healthy controls [4,5,6]
Islet beta cells are the target of immune-mediated attack but it is within secondary lymphoid organs that lymphocytes are primed with their cognate antigen to initiate humoral and T cell responses [8, 9]
Summary
Type 1 diabetes develops as a result of the immune-mediated destruction of insulin-secreting beta cells in the islets of Langerhans of the pancreas. Evidence of insulitis has been reported in histological pancreas specimens from donors with recent-onset type 1 diabetes, along with a marked reduction in islets that stain positively for insulin compared with specimens from healthy controls [4,5,6]. Islet beta cells are the target of immune-mediated attack but it is within secondary lymphoid organs that lymphocytes are primed with their cognate antigen to initiate humoral and T cell responses [8, 9]. Lymph nodes are highly organised structures that are densely populated with supportive stromal cells, antigen-presenting dendritic cells, macrophages and migrating lymphocytes. Human lymph nodes consist of an outer capsule; a cortex of B cell follicles (outer zone) and T cells (inner zone); the medulla, through which medullary sinuses branch, facilitating the migration of cells; and the hilum, through which the lymph fluid exits the lymph node to flow through lymphatic vessels that connect each of the lymph nodes
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