Klatka Maria, Kaszubowska Lucyna, Grywalska Ewelina, Wasiak Magdalena, Szewczyk Leszek, Foerster Jerzy, Cyman Marta, Rolinski Jacek
Department of Clinical Immunology and Immunotherapy, Medical University of Lublin, Lublin, Poland.
Folia Histochem Cytobiol. 2014;52(1):69-77. doi: 10.5603/FHC.2014.0008.
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.
儿童甲状腺功能亢进症几乎所有病例都由格雷夫斯病（GD）引起。最近的研究证实了调节性T细胞（Tregs）在自身免疫性疾病发展中的重要作用。然而，GD中T细胞反应与Treg增殖之间的相互作用仍知之甚少。本研究的目的是评估从50例GD患儿分离的Treg细胞（Tregs）和CD3 + T淋巴细胞在使用抗甲状腺药物甲巯咪唑（MMI）治疗前后的增殖情况。通过甲基 - 3H - 胸腺嘧啶核苷掺入法测量，将用丝裂原佛波醇12 - 肉豆蔻酸酯13 - 乙酸酯（PMA）刺激的CD3 +细胞和Tregs的增殖率与未刺激细胞的增殖率进行比较。MMI治疗前，PMA刺激和未刺激的CD3 +细胞的增殖率均显著高于治疗后。同时，MMI治疗前，PMA刺激和未刺激的Tregs的增殖率均显著较低。此外，我们观察到在MMI治疗开始前和治疗后，甲状腺功能亢进症无复发的患者中，未刺激和PMA刺激的Tregs的细胞增殖率较高。MMI治疗前CD3 +细胞增殖率与外周血游离三碘甲状腺原氨酸（fT3）以及游离甲状腺素（fT4）浓度之间存在正相关。MMI治疗前后CD3 + T细胞的增殖率与促甲状腺素受体抗体（TSI）指数呈正相关。因此，与CD3 + T细胞相比，患有格雷夫斯病的儿童表现出较低的Tregs增殖潜力。CD3 + T细胞和Tregs的共培养表明，Tregs在GD患者中不能有效抑制CD3 + T细胞的增殖。结论。MMI治疗降低了儿童GD患者CD3 + T细胞的增殖活性，并提高了Tregs的增殖率。我们认为GD疾病中部分功能失调的Treg细胞可能受到CD3 + T细胞的抑制，并且甲巯咪唑发挥了一些免疫调节作用。
