title: Treatment of Graves' disease with methimazole in children alters the proliferation of Treg cells and CD3+ T lymphocytes.
abstract: Almost all cases of hyperthyroidism in children result from Graves' disease (GD). Recent studies have confirmed a significant role of T regulatory cells (Tregs) in the development of autoimmune diseases. However, the interactions between T cell responses and Treg proliferation in GD are still poorly understood. The aim of this study was to assess the proliferation of Treg cells (Tregs) and CD3+ T lymphocytes isolated from 50 children with GD before and after treatment with the thyreostatic drug methimazole (MMI). The proliferation rates, measured by methyl-3H-thymidyne incorporation, of CD3+ cells and Tregs stimulated with mitogen phorbol 12-myristate 13-acetate (PMA) were compared with those of unstimulated cells. The proliferation rates of both PMA-stimulated and unstimulated CD3+ cells prior to treatment with MMI were significantly higher than after treatment. Simultaneously, the proliferation rates of both PMA-stimulated and unstimulated Tregs were significantly lower before MMI treatment. Moreover, we observed higher cell proliferation rates of unstimulated and PMA-stimulated Tregs before the initiation of MMI therapy and after treatment in patients who had no relapse of hyperthyroidism. There was a positive correlation between the CD3+ cells proliferation rate before MMI treatment and fT3, as well as fT4 concentration in peripheral blood. The proliferation rates of CD3+ T cells before and after MMI treatment positively correlated with the TSI index. Thus, children suffering from Graves' disease presented lower Tregs proliferative potential compared with CD3+ T cells. Cocultures of CD3+ T cells and Tregs showed that Tregs were not capable of efficiently inhibiting the proliferation of CD3+ T cells in GD patients. Conclusions. MMI treatment reduced the proliferative activity of CD3+ T cells in pediatric GD patients and increased the proliferation rate of Tregs. We suggest that Treg cells that are partly dysfunctional in GD disease are probably suppressed by CD3+ T cells and that methimazole exerts some immunomodulatory effects.
authors.forename: Maria
authors.initials: M
authors.lastname: Klatka
authors.forename: Lucyna
authors.initials: L
authors.lastname: Kaszubowska
authors.affiliation: Department of Clinical Immunology and Immunotherapy, Medical University of Lublin, Lublin, Poland. ewelina.grywalska@gmail.com.
authors.forename: Ewelina
authors.initials: E
authors.lastname: Grywalska
authors.forename: Magdalena
authors.initials: M
authors.lastname: Wasiak
authors.forename: Leszek
authors.initials: L
authors.lastname: Szewczyk
authors.forename: Jerzy
authors.initials: J
authors.lastname: Foerster
authors.forename: Marta
authors.initials: M
authors.lastname: Cyman
authors.forename: Jacek
authors.initials: J
authors.lastname: Rolinski
mesh_terms: D000293:Adolescent; D013956:Antithyroid Agents / Q000627:therapeutic use*; D017252:CD3 Complex / Q000378:metabolism; D016022:Case-Control Studies; D049109:Cell Proliferation / Q000187:drug effects*; D002478:Cells, Cultured; D002648:Child; D005260:Female; D006111:Graves Disease / Q000188:drug therapy* / Q000276:immunology*; D006801:Humans; D018655:Lymphocyte Count; D008713:Methimazole / Q000627:therapeutic use*; D013601:T-Lymphocytes / Q000187:drug effects* / Q000502:physiology; D050378:T-Lymphocytes, Regulatory / Q000187:drug effects* / Q000502:physiology
chemical_list: D013956:Antithyroid Agents; D017252:CD3 Complex; D008713:Methimazole