Islet inflammation and CXCL10 in recent‐onset type 1 diabetes

Type 1 diabetes results from a T cell‐mediated destruction of insulin‐producing pancreatic β cells. Little is known on local factors contributing to migration of T cells to pancreatic tissue. We recently demonstrated evidence of viral infection in β cells in several recent‐onset type 1 diabetes patients. Islet inflammation was analysed in a series of new‐ or recent‐onset type 1 diabetic patients and non‐diabetic control subjects. Autoimmune T cell reactivity was studied in lymphocytes derived from pancreas‐draining lymph nodes of one recent‐onset type 1 diabetes patient in partial clinical remission. Insulitic lesions were characterized by presence of β cells, elevated levels of the chemokine CXCL10 and infiltration of lymphocytes expressing the corresponding chemokine receptor CXCR3 in all pancreatic lesions of type 1 diabetes patients, regardless of enterovirus infection of β cells. CXCR3 and CXCL10 were undetectable in pancreata of non‐diabetic control subjects. T cells isolated from draining lymph nodes of a recent‐onset patient with virally infected β cells and in clinical remission reacted with multiple islet autoantigens and displayed a mixed interferon (IFN)‐γ/interleukin (IL)‐10 cytokine pattern. Our data point to CXCL10 as an important cytokine in distressed islets that may contribute to inflammation leading to insulitis and β cell destruction, regardless of local viral infection. We demonstrate further pro‐ and anti‐inflammatory islet autoreactivity, indicating that different adaptive and innate immune responses may contribute to insulitis and β cell destruction.