open access

Vol 52, No 1 (2014)
Original paper
Submitted: 2014-02-19
Accepted: 2014-04-08
Published online: 2014-05-07
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Treatment of Graves’ disease with methimazole in children alters the proliferation of Treg cells and CD3+ T lymphocytes

Maria Klatka, Lucyna Kaszubowska, Ewelina Grywalska, Magdalena Wasiak, Leszek Szewczyk, Jerzy Foerster, Marta Cyman, Jacek Rolinski
DOI: 10.5603/FHC.2014.0008
·
Folia Histochem Cytobiol 2014;52(1):69-77.

open access

Vol 52, No 1 (2014)
ORIGINAL PAPERS
Submitted: 2014-02-19
Accepted: 2014-04-08
Published online: 2014-05-07

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. (Folia Histochemica et Cytobiologica 2014, Vol. 52, No. 1, 69–77)

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. (Folia Histochemica et Cytobiologica 2014, Vol. 52, No. 1, 69–77)

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Keywords

children; Graves’ disease; lymphocyte proliferation; methimazole; T cells; Treg cells; PMA

About this article
Title

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

Journal

Folia Histochemica et Cytobiologica

Issue

Vol 52, No 1 (2014)

Article type

Original paper

Pages

69-77

Published online

2014-05-07

DOI

10.5603/FHC.2014.0008

Bibliographic record

Folia Histochem Cytobiol 2014;52(1):69-77.

Keywords

children
Graves’ disease
lymphocyte proliferation
methimazole
T cells
Treg cells
PMA

Authors

Maria Klatka
Lucyna Kaszubowska
Ewelina Grywalska
Magdalena Wasiak
Leszek Szewczyk
Jerzy Foerster
Marta Cyman
Jacek Rolinski

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