EFFECTS OF HELPER AND REGULATORY CELLS UPON PHENOTYPIC COMPOSITION OF BLOOD B LYMPHOCYTES AND THYROID GLAND IN GRAVES’ DISEASE
https://doi.org/10.15789/1563-0625-2018-3-431-438
Abstract
The aim of this work was a comparative study of the helper- (Th cells) and regulatory T cells (Treg) effects upon the phenotypic composition of B lymphocytes in blood and thyroid tissue in Graves’ disease (GD). 43 women with GD were examined. The diagnosis of GD was based on clinical and laboratory signs of the disease: complaints, clinical picture of the thyrotoxicosis with objective examination, characteristic sonographic changes in thyroid gland, as well as elevated titers of antibodies to thyroid-stimulating hormone receptor in blood serum, and corresponding changes in thyroid status. 67 practically healthy women were examined as a control. The studies of Th cells, Treg and B lymphocytes phenotypes in blood and thyroid tissue were carried out by flow cytometry using direct immunofluorescence, respectively, in whole peripheral blood and lymphocytes isolated from thyroid tissue. The relative amounts of Tregs in thyroid gland from the patients with GD corresponds to their level in the blood. We did not find any changes in the content of blood T helpers expressing vs. non-expressing CD25 receptors, as compared to the control values. In patients with GD, an increased B1 cells content was revealed in peripheral blood. The percentage of this B cell subpopulation in thyroid tissue is reduced when compared to the levels found in blood, but with increased memory B cells contents. The number of activated B lymphocytes (by CD23 marker) in blood of patients with GD is reduced when compared to control values. It was found that, in thyroid tissue, there is an even more pronounced decrease in the relative amount of activated B cells compared to the levels detected in blood from these patients. By means of correlation analysis, it was found that increase in activated B lymphocytes in blood from controls is accompanied by a co-directional reaction from Treg (the usual immunoregulatory process). In Graves’ disease, such a relationship was not found. The amounts of Treg and activated T helper cells in blood of the patients did positively correlate with common B lymphocytes, B2 cells and na ve B lymphocytes. Meanwhile, Treg’s in thyroid tissue, were completely excluded from the system of interactions with activated B lymphocytes. It is assumed that a decrease in Treg’s content in peripheral blood, along with altered functional activity is observed in patients with GD.
About the Authors
A. A. SavchenkoRussian Federation
PhD, MD (Medicine), Professor, Head, Laboratory of Cellular and Molecular Physiology and Pathology, Research Institute of Medical Problems of the North, KRC SB RAS; Head, Physiology Department KSV.F. Voino-Yasenetsky MU
M. A. Dudina
Russian Federation
A. G. Borisov
Russian Federation
PhD (Medicine), Leading Research Associate, Laboratory of Cellular and Molecular Physiology and Pathology, Research Institute of Medical Problems of the North, KRC SB RAS; Associate Professor, Department of Infectious Diseases KSV.F. Voino-Yasenetsky MU
S. A. Dogadin
Russian Federation
PhD (Medicine), Assistant Professor, Department of Internal Medicine
I. V. Kudryavtsev
Russian Federation
Kudryavtsev Igor V. - PhD (Biology), Senior Research Associate, Department of Immunology IEM; Assistant Professor, Department of Immunology, Pavlov First St. Petersburg State I. Pavlov MU.
197376, St. Petersburg, Acad. Pavlov str., 12, phone: 7 (812) 234-29-29
A. V. Moshev
Russian Federation
Junior Research Associate, Laboratory of Cellular and Molecular Physiology and Pathology
V. А. Mankovskiy
Russian Federation
Clinical Surgeon, The Surgery Department No. 2.
Krasnoyarsk
References
1. Vanushko V.E., Fadeev V.V. Graves’ disease (clinical lecture). Endokrinnaya khirurgiya = Endocrine Surgery, 2013, no. 1, pp. 23-33. (In Russ.)
2. Kudryavtsev I.V., Subbotovskaya A.I. Application of six-color flow cytometric analysis for immune profile monitoring. Meditsinskaya immunologiya = Medical Immunology (Russia), 2015, Vol. 17, no. 1, pp. 19-26. (In Russ.) doi: 10.15789/1563-0625-2015-1-19-26.
3. Savchenko A.A., Dogadin S.A., Dudina M.A., Matsynina V.P. The clinical and immunological indices and their interaction with thyroid status in patients with Graves’ disease depending on thyrocytes peroxidase autoantibodies level. Problemy endokrinologii = Problems of Endocrinology, 2016, Vol. 62, no. 1, pp. 4-9. (In Russ.) doi: 10.14341/probl20166214-9.
4. Dhaliwal B., Pang M.O., Keeble A.H., James L.K., Gould H.J., McDonnell J.M., Sutton B.J., Beavil A.J. IgE binds asymmetrically to its B cell receptor CD23. Sci. Rep., 2017, Vol. 7, p. 45533.
5. Eshaghkhani Y., Sanati M.H., Nakhjavani M., Safari R., Khajavi A., Ataei M., Jadali Z. Disturbed Th1 and Th2 balance in patients with Graves’ disease. Minerva Endocrinol., 2016, Vol. 41, no. 1, pp. 28-36.
6. Hu Y., Tian W., Zhang L.L., Liu H., Yin G.P., He B.S., Mao X.M. Function of regulatory T-cells improved by dexamethasone in Graves’ disease. Eur. J. Endocrinol., 2012, 166, Vol. 4, pp. 641-646.
7. Klatka M., Grywalska E., Partyka M., Charytanowicz M., Kiszczak-Bochynska E., Rolinski J. Th17 and Treg cells in adolescents with Graves’ disease. Impact of treatment with methimazole on these cell subsets. Autoimmunity, 2014, Vol. 47, no. 3, pp. 201-211.
8. Kurozumi A., Okada Y., Arao T., Narisawa M., Torimoto K., Yamamoto S., Tanaka Y. Induction of thyroid remission using rituximab in a patient with type 3 autoimmune polyglandular syndrome including Graves’ disease and type 1 diabetes mellitus: a case report. Endocr. J., 2015, Vol. 62, no. 1, pp. 69-75.
9. Maecker H., McCoy P., Nussenblatt R. Standardizing immunophenotyping for the human immunology project. Nat. Rev. Immunol., 2012, Vol. 12, pp. 191-200.
10. Pawlowski P., Grubczak K., Kostecki J., Ilendo-Poskrobko E., Moniuszko M., Pawlowska M., Rejdak R., Reszec J., Mysliwiec J. Decreased frequencies of peripheral blood CD4+CD25+CD127-Foxp3+ in patients with Graves’ disease and Graves orbitopathy: Enhancing effect of insulin growth factor-1 on Treg cells. Horm. Metab. Res., 2017, Vol. 49, no. 3, pp. 185-191.
11. Peng D., Xu B., Wang Y., Guo H., Jiang Y. A high frequency of circulating Th22 and Th17 cells in patients with new onset Graves’ disease. PLoS ONE, 2013, Vol. 8, no. 7, e68446. doi: 10.1371/journal.pone.0068446.
12. Segundo C., Rodríguez C., García-Poley A., Aguilar M., Gavilán I., Bellas C., Brieva J.A. Thyroid-infiltrating B lymphocytes in Graves’ disease are related to marginal zone and memory B cell compartments. Thyroid, 2001, Vol. 11, no. 6, pp. 525-530.
13. Smith T.J., Hegedüs L. Graves’ disease. N. Engl. J. Med., 2016, Vol. 375, no. 16, pp. 1552-1565.
14. Song R.H., Yu Z.Y., Qin Q., Wang X., Muhali F.S., Shi L.F., Jiang W.J., Xiao L., Li D.F., Zhang J.A. Different levels of circulating Th22 cell and its related molecules in Graves’ disease and Hashimoto’s thyroiditis. Int. J. Clin. Exp. Pathol., 2014, Vol. 7, no. 7, pp. 4024-4031.
15. Yuan Q., Zhao Y., Zhu X., Liu X. Low regulatory T cell and high IL-17 mRNA expression in a mouse Graves’ disease model. J. Endocrinol. Invest., 2017, Vol. 40, no. 4, pp. 397-407.
Review
For citations:
Savchenko A.A., Dudina M.A., Borisov A.G., Dogadin S.A., Kudryavtsev I.V., Moshev A.V., Mankovskiy V.А. EFFECTS OF HELPER AND REGULATORY CELLS UPON PHENOTYPIC COMPOSITION OF BLOOD B LYMPHOCYTES AND THYROID GLAND IN GRAVES’ DISEASE. Medical Immunology (Russia). 2018;20(3):431-438. (In Russ.) https://doi.org/10.15789/1563-0625-2018-3-431-438