Function of regulatory T-cells improved by dexamethasone in Graves' disease

Hu, Yun; Tian, Wei; Zhang, Lingling; Líu, Hao; Yin, Guoyong; He, Bangshun; Mao, Xiao‐Ming

doi:10.1530/eje-11-0879

Cited by 30 publications

(34 citation statements)

References 28 publications

(31 reference statements)

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“…Moreover, Treg cell function appeared to be impaired in patients with GD. It has also [4]. The immunosuppressive properties of DEX were also used to improve the effects of methimazole treatment by Mao et al [25].…”

Section: Discussionmentioning

confidence: 99%

“…Defects in their function may result in chronic autoimmunity [7][8][9][10][11]. The impaired function of Treg cells in patients with Graves' disease has also been reported [4]. Moreover, depletion of CD4+CD25+ T cells enhances the development of Graves' hyperthyroidism in the mouse model [12].…”

Section: Introductionmentioning

confidence: 94%

“…Treg cells are a subset of CD4+ T cells that express high levels of the CD25 molecule and transcription factor forkhead box P3 (FOXP3). Treg cells make up 5-10% of peripheral CD4+ T cells [4] and can be divided into two subpopulations: the first subpopulation comprises naturally occurring nTreg cells (which emerge de novo from the embryonic/neonatal thymus and are also described as "thymic" Tregs or tTregs), whereasthe second one consists of inducible iTreg cells (induced in the periphery, and also described as "peripheral" Tregs or pTregs), whose function is to acquire a regulatory phenotype in response to pathogens and inflammation [5]. Treg cells exert a key homeostatic effect on two subpopulations of T helper (Th) cells, Th1 and Th2.…”

Section: Introductionmentioning

confidence: 99%

“…Th1 cells secrete IFNg, IL-2, and IL-12 and are associa ted with cell-mediated immune responses, while Th2 cells secrete IL-4, IL-5, and IL-10 and are involved in humoral immunity. The imbalance between Th1 and Th2 cells caused by Treg cell dysfunction may determine the outcome of autoimmune diseases [4].…”

Section: Introductionmentioning

confidence: 99%

“…Although it lowers the level of thyroid autoantibodies-sometimes leading to long-term remission [4,21,22] -little is known as yet about its influence on human cell-mediated immune response. The aim of our study was to assess in vitro the effects of Treg cells on the proliferation of CD3+ T lymphocytes in various cocultures of cells isolated from the peripheral blood of children with hyperthyreosis arising from Graves' disease, and to describe the impact of MMI treatment on the proliferation of those cells.…”

Section: Introductionmentioning

confidence: 99%

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Treatment of Graves’ disease with methimazole in children alters the proliferation of Treg cells and CD3+ T lymphocytes

Klatka

Kaszubowska

Grywalska

et al. 2014

Folia Histochem Cytobiol.

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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.

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Section: Discussionmentioning

confidence: 99%