title: 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.
authors.affiliation: Department of Pediatrics, Pediatrics I, Medical University Innsbruck , Innsbruck, Austria.
authors.forename: Johannes
authors.initials: J
authors.lastname: Hofer
authors.forename: Sabine
authors.initials: S
authors.lastname: Hofer
authors.forename: Manuela
authors.initials: M
authors.lastname: Zlamy
authors.forename: Verena
authors.initials: V
authors.lastname: Jeller
authors.forename: Christian
authors.initials: C
authors.lastname: Koppelstaetter
authors.forename: Anita
authors.initials: A
authors.lastname: Brandstätter
authors.forename: Hannelore
authors.initials: H
authors.lastname: Kern
authors.forename: Julia
authors.initials: J
authors.lastname: Köhle
authors.forename: Lothar Bernd
authors.initials: LB
authors.lastname: Zimmerhackl
authors.forename: Martina
authors.initials: M
authors.lastname: Prelog
mesh_terms: D000293:Adolescent; D018414:CD8-Positive T-Lymphocytes / Q000378:metabolism; D016022:Case-Control Studies; D002648:Child; D003922:Diabetes Mellitus, Type 1 / Q000097:blood / Q000378:metabolism*; D006801:Humans; D007328:Insulin / Q000378:metabolism; D015851:Interleukin-7 / Q000378:metabolism; D017493:Leukocyte Common Antigens / Q000096:biosynthesis; D007963:Leukocytes, Mononuclear / Q000166:cytology; D011948:Receptors, Antigen, T-Cell / Q000378:metabolism; D016176:T-Lymphocyte Subsets / Q000276:immunology*; D013601:T-Lymphocytes / Q000166:cytology; D016615:Telomere / Q000648:ultrastructure; D013950:Thymus Gland / Q000378:metabolism*
chemical_list: D007328:Insulin; D015851:Interleukin-7; D011948:Receptors, Antigen, T-Cell; D017493:Leukocyte Common Antigens