Insulitis in type 1 (insulin‐dependent) diabetes mellitus in man—macrophages, lymphocytes, and interferon‐γ containing cells

Abstract

This study sought to determine, firstly, the relative frequency of lymphocytes and macrophages and, secondly, the percentage of lymphocytes containing interferon-gamma in inflamed islets (insulitis) of patients with type 1 (insulin-dependent) diabetes. Autopsy pancreases of 12 patients who had died of recent-onset type 1 diabetes and one pre-diabetic patient who had died of cardiomyopathy were examined immunohistochemically. In the 87 islets that were studied, the lymphocyte macrophage ratio was 9.7:1 and approximately 40 per cent of the lymphocytes contained interferon-gamma. Interferon-gamma release in the insulitis process may be involved in the pathogenesis of type 1 diabetes.

Cytokine overproduction in healthy first degree relatives of patients with IDDM

“…By contrast, production of type 2 cytokines (IL-4 and IL-10) was not raised, in keeping with the proposal that a T helper 1 dominant immune response plays a central role in disease pathogenesis [15,10]. Because of obvious difficulty in obtaining tissue samples, study of local cytokine production in human pancreata has been limited [16,17]. We have demonstrated, how- Diabetologia (1998) Summary Healthy family members of patients with insulin-dependent diabetes mellitus (IDDM) are known to share a number of immunological abnormalities with their affected relatives.…”

Altered immune response to insulin in newly diagnosed compared to insulin-treated diabetic patients and healthy control subjects

“…Even though autoantibodies may not be directly involved in the destructive process, 60 % of new-onset diabetic patients are positive for insulin autoantibodies (IAA) compared to only 0.5 % of healthy control subjects [2]. The involvement of T cells in the pathogenesis has been implicated by insulitis [13], the recurrence of insulitis and diabetes after pancreas transplantation [14] and the transfer of diabetes with non-T-cell-depleted bone marrow transplants …”

Apportioning Blame: Autoreactive CD4+ and CD8+ T Cells in Type 1 Diabetes

“…CD8 + cytotoxic T lymphocytes were the more abundant T lymphocytes present in the insulitic infiltrations (Foulis et al 1991;Itoh et al 1993;Willcox et al 2009). Moreover, class I human leukocyte antigen (HLA) is hyper-expressed in islet and endothelial cells in the majority of pancreatic biopsies from patients presenting with insulitis, and even in up to 20% of pancreatic biopsies from patients without insulitis (Itoh et al 1993).…”