World Journal of Pediatrics

, Volume 9, Issue 3, pp 245–250 | Cite as

The differences in T and B cell subsets in thyroid of children with Graves’ disease and Hashimoto’s thyroiditis

  • Iwona Ben-SkowronekEmail author
  • Leszek Szewczyk
  • Beata Kulik-Rechberger
  • Elzbieta Korobowicz
Original Article



The differences between Graves’ disease (GD) and Hashimoto’s thyroiditis (HT) suggest that changes in the subsets of T cells may have an influence on the course of these reactions.


This study included 90 children: 30 with GD, 30 with HT, and 30 healthy children as controls. After thyroidectomy, standard histological examinations and immunohistochemical reactions were performed in paraffin specimens with monoclonal antibodies against T cell markers CD3, CD4, CD8 as well as against CD79 alpha B cells. Ultrathin sections were examined under a transmission electron microscope.


Autoimmune reaction in GD consisted of an increased number of CD4+ T cells (3.17±4.27%) and plasma cells (22.89±8.61%) producing thyroidstimulating hormone-receptors and stimulating thyrocytes to activity. The number of CD8+ T cells was increased in children with HT (20.54±0.68%) as compared with the controls (0.65±0.30%). The autoimmune reaction in the HT children showed antibody dependent cytotoxicity with a low number of CD4+ T cells and an increased number of CD8+ T cells in the thyroid tissue in comparison with that in the GD children and the controls. Plasma cells (31.65±9.11%) in this situation produced the antibodies involved in cytotoxic reactions against thyrocytes.


Graves’ disease is characterized by the increased number of CD4+ T cells and CD8+ T cells. Hashimoto’s thyroiditis is characterized by the low number of CD4+ T cells and increased number of CD8+ T cells. CD8+ T cells have cytotoxic properties only in Hashimoto’s thyroiditis.

Key words

autoimmunity lymphocytes thyroid disorders 


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  1. 1.
    Marinò M, Chiovato L, Friedlander JA, Latrofa F, Pinchera A, McCluskey RT. Serum antibodies against megalin (GP330) in patients with autoimmune thyroiditis. J Clin Endocrinol Metab 1 1999:84:2468–2474.CrossRefGoogle Scholar
  2. 2.
    Weetman AP. Autoimmune thyroid disease. Autoimmunity 2004;37:337–340.PubMedCrossRefGoogle Scholar
  3. 3.
    Di Cerbo A, Di Paola R, Menzaghi C, De Filippis V, Tahara K, Corda D, et al. Graves’ immunoglobulins activate phospholipase A by recognizing specific epitopes on thyrotropin receptor. J Clin Endocrinol Metab 1999;84:3283–3292.PubMedCrossRefGoogle Scholar
  4. 4.
    Evans C, Morgenthaler NG, Lee S, Llewellyn DH, Clifton-Bligh R, John R, et al. Development of a luminescent bioassay for thyroid stimulating antibodies. J Clin Endocrinol Metab 1999;84: 374–377.PubMedCrossRefGoogle Scholar
  5. 5.
    Endo K, Kasagi K, Konishi J, Ikekubo K, Okuno T, Takeda Y, et al. Detection and properties of TSH-binding inhibitor immunoglobulins in patients with Graves’ disease and Hashimoto’s Thyroiditis. J Clin Endocrinol Metab 1978;46:734–739.PubMedCrossRefGoogle Scholar
  6. 6.
    Morshed SA, Latif R, Davies TF. Characterization of thyrotropin receptor antibody-induced signaling cascades. Endocrinology 2009;150:519–529.PubMedCrossRefGoogle Scholar
  7. 7.
    Pan D, Shin YH, Gopalakrishnan G, Hennessey J, De Groot LJ. Regulatory T-cells in Graves’ disease. Clin Enocrinol (Oxf) 2009;71:587–593.CrossRefGoogle Scholar
  8. 8.
    Weetman AP. Diseases associated with thyroid autoimmunity: explanations for the expanding spectrum. Clin Endocrinol (Oxf) 2011;74:411–418.CrossRefGoogle Scholar
  9. 9.
    Bossowski A, Moniuszko M, Dąbrowska M, Mrugacz M, Sawicka B, Bossowska A, et al. Analysis of T regulatory cells in the peripheral blood in children and adolescents with Graves’ disease and Hashimoto’s thyroiditis. Pediatric Endocrinol 2011;1:37–48.Google Scholar
  10. 10.
    Braley-Mullen H, Sharp GC. Adoptive transfer murine model of granulomatous experimental autoimmune thyroiditis. Int Rev Immunol 2000;19:535–555.PubMedCrossRefGoogle Scholar
  11. 11.
    Marazuela M, Steegman JL. Transfer of autoimmune hypothyroidism following bone marrow transplantation from a donor with Graves’disease. Bone Marrow Transplant 2000;26:1217–1220.PubMedCrossRefGoogle Scholar
  12. 12.
    Ng HP, Kung AW. Induction of autoimmune thyroiditis and hypothyroidism by immunization of immunoactive T cell epitope of thyroid peroxidase. Endocrinology 2006;147:3085–3092.PubMedCrossRefGoogle Scholar
  13. 13.
    Ng HP, Banga JP, Kung AW. Development of a murine model of autoimmune thyroiditis induced with homologous mouse thyroid peroxidase. Endocrinology 2004;145:809–816.PubMedCrossRefGoogle Scholar
  14. 14.
    Morris GP, Kong YC. Interference with CD4+CD25+ T-cellmediated tolerance to experimental autoimmune thyroiditis by glucocorticoid-induced tumor necrosis factor receptor monoclonal antibody. J Autoimmun 2006;26:24–31.PubMedCrossRefGoogle Scholar
  15. 15.
    Morris GP, Chen L, Kong YC. CD137 signaling function of CD4+CD25+ regulatory T-cells in induced tolerance to experimental immune thyroiditis. Cell Immunol 2003;226:20–29.PubMedCrossRefGoogle Scholar
  16. 16.
    Drabko K, Winnicka D, Gaworczyk A, Beń-Skowronek I, Skomra D, Kowalczyk JR. Donor origin of Graves’ disease i BMT recipient: evidence from FISH studies of thyroid tissue. Bone Marrow Transplant 2 2006;37:789–791.CrossRefGoogle Scholar
  17. 17.
    Tsujio M, Watahiki Y, Yoshioka K, Mutoh K. Morphology of thyroid follicular cells of methimazole-treated rats. Anat Histol Embryol 2007;36:290–294.PubMedCrossRefGoogle Scholar
  18. 18.
    Hornung MW, Degitz SJ, Korte LM, Olson JM, Kosian PA, Linnum AL, et al. Inhibition of thyroid hormone release from cultured amphibian thyroid glands by methimazole, 6-propylthiouracil, and perchlorate. Toxicol Sci 2010;118:42–51.PubMedCrossRefGoogle Scholar
  19. 19.
    Piccirillo CA, Shevach EM. Naturally occurring CD4+CD25+ immunoregulatory cells: central players In the arena of peripheral tolerance. Semin in Immunol 2004;16:81–88.CrossRefGoogle Scholar
  20. 20.
    Shevach EM. From vanilla to 28 flavors: multiple varieties of T regulatory cells. Immunity 2006;25:195–201.PubMedCrossRefGoogle Scholar
  21. 21.
    Zantut-Wittmann DE, Tambascia MA, da Silva Trevisan MA, Pinto GA, Vassallo J. Antithyroid drugs inhibit in vivo HLA-DR expression in thyroid follicular cells in Graves’ disease. Thyroid 2001;11:575–580.PubMedCrossRefGoogle Scholar
  22. 22.
    Enk AH. CD4+CD25+ Treg cells - the renaissance of suppressor T cells? Nature Rev Immunology 2003;3:3.Google Scholar
  23. 23.
    Stassi G, De Maria R. Autoimmune thyroid disease: new model of cell health in autoimmunity. Nat Rev Immunol 2002;2:195–204.PubMedCrossRefGoogle Scholar
  24. 24.
    Gardella S, Andrei C, Lotti LV, Poggi A, Torrisi MR, Zocchi MR, et al. CD8(+) T lymphocytes inducpolarized exocytosis of secretory lysosomes by dendriti cells with release of interleukn 1β and cathepsin D. Blood 2 2001;98:2152–2159.CrossRefGoogle Scholar
  25. 25.
    Negrini S, Fenoglio D, Balestra P, Fravega M, Filaci G, Indiveri F. Endocrine regulation of suppressor lymphocytes: role of the glucocorticoid-induced TNF-like receptor. Ann N Y Acad Sci 2006;1069:377–385.PubMedCrossRefGoogle Scholar
  26. 26.
    Kishimoto T, Goyert S, Kikutani H, Mason D, Miyasaka M, Moretta L, et al. CD antigens 1996. Blood 1997;89:3502.PubMedGoogle Scholar
  27. 27.
    Kishimoto T, Goyert S, Kikutani H, Mason D, Miyasaka M, Moretta L, et al. Update of CD antigens, 1996. J Immunol 1997;158:3035–3036.PubMedGoogle Scholar
  28. 28.
    Kishimoto T, Goyert S, Kikutani H, Mason D, Miyasaka M, Moretta L, et al. Update: new CD antigens, 1996. Tissue Antigens 1997;49:287–288.PubMedCrossRefGoogle Scholar
  29. 29.
    Armengol MP, Juan M, Lucas-Martín A, Fernández-Figueras MT, Jaraquemada D, Gallart T, et al. T Thyroid autoimmune disease: demonstration of thyroid antigen-specific B cells and recombination-activating gene expression in chemokinecontaining active intrathyroidal germinal centers. A Am J Pathol 20 2001;159:861–873CrossRefGoogle Scholar
  30. 30.
    Bossowski A, Urban M, Stasiak-Barmuta A. Analysis of changes in the percentage of B (CD19) and T (CD3) lymphocytes, subsets CD4, CD8 and their memory (CD45RO), and naive (CD45RA) T cells in children with immune and non-immune thyroid diseases. J Pediatr Endocrinol Metab 2003;16:63–70.PubMedCrossRefGoogle Scholar
  31. 31.
    Iwona BS, Jadwiga SS, Elzbieta K, Leszek S. Lymphocytes in peripheral blood and thyroid tissue in children with Graves’ disease. World J Pediatr 2008;4:274–282.PubMedCrossRefGoogle Scholar
  32. 32.
    Hidaka Y, Amino N, Iwatani Y, Kaneda T, Nasu M, Mitsuda N, et al. Increase in peripheral natural killer cell activity in patients with autoimmune thyroid disease. Autoimmunity 1992;11:239–246.PubMedCrossRefGoogle Scholar

Copyright information

© Children's Hospital, Zhejiang University School of Medicine and Springer-Verlag Berlin Heidelberg 2013

Authors and Affiliations

  • Iwona Ben-Skowronek
    • 1
    Email author
  • Leszek Szewczyk
    • 1
  • Beata Kulik-Rechberger
    • 2
  • Elzbieta Korobowicz
    • 3
  1. 1.Department of Pediatric Endocrinology and DiabetologyMedical UniversityLublinPoland
  2. 2.Department of Neonatology and Infant PathologyMedical UniversityLublinPoland
  3. 3.Department of PathologyMedical UniversityLublinPoland

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