Elevated Proportions of Recent Thymic Emigrants in Children and Adolescents with Type 1 Diabetes

Abstract

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 naïve 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 naïve T cell subset and its TREC content, relative telomere length (RTL) of naïve 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 naïve T cell compartment. The ability of the immune system to reconstitute the naïve 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.

Decreased microRNA miR-181c expression in peripheral blood mononuclear cells correlates with elevated serum levels of IL-7 and IL-17 in patients with myasthenia gravis

“…Consequently, IL-7 plays a pathogenic role in multiple autoimmune diseases, including rheumatoid arthritis (RA) [28,29], inflammatory bowel disease (IBD) [30], psoriasis [31], spondylarthritis [32], and type 1 diabetes [33].…”

Immune Aging and Autoimmune Diseases in Children

“…To consider this definition of RTE, a study of 70 JIA patients (8 systemic onset, 10 polyarticular rheumatoid factor-positive, 12 polyarticular rheumatoid factor-negative, 27 persistent oligoarticular, 7 extended oligoarticular, 4 psoriatic and 2 enthesitis-associated JIA) analyzed TREC amounts in CD4+CD45RA+CD31+ T cells [18]. Following a mathematical model [80], the authors [78] calculated TRECs/ml blood as it directly reflects the reduction in thymic output and is not influenced by the dynamics of either TREC+ and TREC-cells.…”

“…Thus, more studies on early onset autoimmunity in children are needed in order to understand the mechanisms of T cell production and peripheral T cell maintenance under autoimmune conditions. Recent studies suggest that a disturbed T cell homeostasis with alterations mimicking the immunological findings of elderly people or adult patients with autoimmune diseases may be of relevance in the early stages of juvenile idiopathic arthritis (JIA) [15][16][17] and diabetes mellitus type I (T1DM) [18]. However, as autoimmunity is a multifactorial process, premature immunosenescence is certainly not the only mechanism that can induce autoimmunity in children.…”

Increased concentration of T‐cell receptor rearrangement excision circles (TREC) in peripheral blood in Graves' disease

“…The only disease which apparently did not follow this pattern being associated with increased thymic activity was myasthenia gravis (MG) and type 1 diabetes mellitus (T1DM). Whereas in MG the increased thymic activity is likely to be pathogenic (see ), in T1DM, the observed increase in TREC concentration was tentatively attributed to thymic stimulation by insulin treatment . These observations suggest that increased rate of thymic senescence could be an important feature of autoimmunity.…”