Elevated proportions of recent thymic emigrants in children and adolescents with type 1 diabetes

摘要

It is unclear, whether pediatric patients with type 1 diabetes (T1DM) show immunological alterations typically found in autoimmune conditions resembling immune dysfunction of the thymus, such as decrease of na?ve T cells, lower T cell receptor excision circle (TREC) numbers, telomeric erosion, and diminished interleukin-7 (IL-7) levels. Furthermore, it is unknown, whether long-term therapy with insulin, a thymic growth factor, interferes with these changes. Therefore, the aim of this study was to analyze the quantity of the na?ve T cell subset and its TREC content, relative telomere length (RTL) of na?ve T cells, and peripheral IL-7 levels in patients with recent-onset T1DM (n = 5), long-standing T1DM (n = 33), and age-matched healthy donors (HD) (n = 37). In long-standing T1DM, TREC numbers/CD8+CD45RA+ T cells were enhanced (p 0.01) compared to HD and correlated with disease duration (p 0.02), an independent factor for increased thymic output (p 0.01), and insulin dosage at blood withdrawal (p 0.05). IL-7 serum levels were elevated in long-standing T1DM (p 0.001) and positively correlated with TREC numbers (p 0.01) and disease duration (p 0.0001). RTLs in CD8+CD45RA+ T cells were significantly increased compared to HD (p 0.02). Our data suggest that longterm insulin therapy may serve as a driving factor for thymic function and rejuvenation of the na?ve T cell compartment. The ability of the immune system to reconstitute the na?ve T cell compartment under well-adjusted insulin therapy may be of major importance for recognition of new antigens, response to vaccinations, and defense of infectious complications.