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<article xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" xmlns:ali="http://www.niso.org/schemas/ali/1.0/" article-type="research-article" dtd-version="1.2" xml:lang="en"><front><journal-meta><journal-id journal-id-type="publisher-id">Journal of microbiology, epidemiology and immunobiology</journal-id><journal-title-group><journal-title xml:lang="en">Journal of microbiology, epidemiology and immunobiology</journal-title><trans-title-group xml:lang="ru"><trans-title>Журнал микробиологии, эпидемиологии и иммунобиологии</trans-title></trans-title-group></journal-title-group><issn publication-format="print">0372-9311</issn><issn publication-format="electronic">2686-7613</issn><publisher><publisher-name xml:lang="en">Central Research Institute for Epidemiology</publisher-name></publisher></journal-meta><article-meta><article-id pub-id-type="publisher-id">497</article-id><article-id pub-id-type="doi">10.36233/0372-9311-2019-6-65-71</article-id><article-categories><subj-group subj-group-type="toc-heading" xml:lang="en"><subject>ORIGINAL RESEARCHES</subject></subj-group><subj-group subj-group-type="toc-heading" xml:lang="ru"><subject>ОРИГИНАЛЬНЫЕ ИССЛЕДОВАНИЯ</subject></subj-group><subj-group subj-group-type="article-type"><subject>Research Article</subject></subj-group></article-categories><title-group><article-title xml:lang="en">Subsets of T regulatory cells in patients with IgE-mediated allergy</article-title><trans-title-group xml:lang="ru"><trans-title>Субпопуляции Т-регуляторных клеток у пациентов с IgE-обусловленной аллергией</trans-title></trans-title-group></title-group><contrib-group><contrib contrib-type="author"><contrib-id contrib-id-type="orcid">https://orcid.org/0000-0003-2949-7834</contrib-id><name-alternatives><name xml:lang="en"><surname>Nikolov</surname><given-names>G. S.</given-names></name><name xml:lang="ru"><surname>Николов</surname><given-names>Г. С.</given-names></name></name-alternatives><address><country country="BG">Bulgaria</country></address><bio xml:lang="en"><p>Georgi S. Nikolov, MD PhD, Department «Immunology», Sofia, 1504, Bulgaria</p></bio><bio xml:lang="ru"><p>Николов Георги Стоянов, доцент, отдел «Иммунология», 1504, г. София, Болгария</p></bio><email>labalerg@ncipd.org</email><xref ref-type="aff" rid="aff1"/></contrib><contrib contrib-type="author"><contrib-id contrib-id-type="orcid">https://orcid.org/0000-0003-4708-6887</contrib-id><name-alternatives><name xml:lang="en"><surname>Todorova</surname><given-names>Y. D.</given-names></name><name xml:lang="ru"><surname>Тодорова</surname><given-names>Я. Д.</given-names></name></name-alternatives><address><country country="BG">Bulgaria</country></address><bio xml:lang="en"><p>Sofia, 1504, Bulgaria</p></bio><bio xml:lang="ru"><p>1504, г. София, Болгария</p></bio><xref ref-type="aff" rid="aff1"/></contrib><contrib contrib-type="author"><contrib-id contrib-id-type="orcid">https://orcid.org/0000-0001-8180-4892</contrib-id><name-alternatives><name xml:lang="en"><surname>Nikolova</surname><given-names>M. H.</given-names></name><name xml:lang="ru"><surname>Николова</surname><given-names>М. Х.</given-names></name></name-alternatives><address><country country="BG">Bulgaria</country></address><bio xml:lang="en"><p>Sofia, 1504, Bulgaria</p></bio><bio xml:lang="ru"><p>1504, г. София, Болгария</p></bio><xref ref-type="aff" rid="aff1"/></contrib><contrib contrib-type="author"><contrib-id contrib-id-type="orcid">https://orcid.org/0000-0002-0018-1361</contrib-id><name-alternatives><name xml:lang="en"><surname>Emilova</surname><given-names>R. G.</given-names></name><name xml:lang="ru"><surname>Емилова</surname><given-names>Р. Г.</given-names></name></name-alternatives><address><country country="BG">Bulgaria</country></address><bio xml:lang="en"><p>Sofia, 1504, Bulgaria</p></bio><bio xml:lang="ru"><p>1504, г. София, Болгария</p></bio><xref ref-type="aff" rid="aff1"/></contrib><contrib contrib-type="author"><contrib-id contrib-id-type="orcid">https://orcid.org/0000-0002-9710-1312</contrib-id><name-alternatives><name xml:lang="en"><surname>Hristova</surname><given-names>D. M.</given-names></name><name xml:lang="ru"><surname>Христова</surname><given-names>Д. М.</given-names></name></name-alternatives><address><country country="BG">Bulgaria</country></address><bio xml:lang="en"><p>Sofia, 1431, Bulgaria</p></bio><bio xml:lang="ru"><p>1431, г. София, Болгария</p></bio><xref ref-type="aff" rid="aff2"/></contrib><contrib contrib-type="author"><contrib-id contrib-id-type="orcid">https://orcid.org/0000-0002-3012-1861</contrib-id><name-alternatives><name xml:lang="en"><surname>Kostova-Shahid</surname><given-names>P. J.</given-names></name><name xml:lang="ru"><surname>Костова-Шахид</surname><given-names>П. Й.</given-names></name></name-alternatives><address><country country="BG">Bulgaria</country></address><bio xml:lang="en"><p>Sofia, 1431, Bulgaria</p></bio><bio xml:lang="ru"><p>1431, г. София, Болгария</p></bio><xref ref-type="aff" rid="aff2"/></contrib><contrib contrib-type="author"><contrib-id contrib-id-type="orcid">https://orcid.org/0000-0001-8435-6175</contrib-id><name-alternatives><name xml:lang="en"><surname>Petrunov</surname><given-names>B. N.</given-names></name><name xml:lang="ru"><surname>Петрунов</surname><given-names>Б. Н.</given-names></name></name-alternatives><address><country country="BG">Bulgaria</country></address><bio xml:lang="en"><p>Sofia, 1504, Bulgaria</p></bio><bio xml:lang="ru"><p>1504, г. София, Болгария</p></bio><xref ref-type="aff" rid="aff1"/></contrib></contrib-group><aff-alternatives id="aff1"><aff><institution xml:lang="en">National Center of Infectious and Parasitsic Diseases</institution></aff><aff><institution xml:lang="ru">Национальный центр заразных и паразитных болезней</institution></aff></aff-alternatives><aff-alternatives id="aff2"><aff><institution xml:lang="en">Aleksandrovska University Hospital</institution></aff><aff><institution xml:lang="ru">Александровская больница</institution></aff></aff-alternatives><pub-date date-type="pub" iso-8601-date="2019-12-16" publication-format="electronic"><day>16</day><month>12</month><year>2019</year></pub-date><volume>96</volume><issue>6</issue><issue-title xml:lang="en"/><issue-title xml:lang="ru"/><fpage>65</fpage><lpage>71</lpage><history><date date-type="received" iso-8601-date="2019-12-15"><day>15</day><month>12</month><year>2019</year></date><date date-type="accepted" iso-8601-date="2019-12-15"><day>15</day><month>12</month><year>2019</year></date></history><permissions><copyright-statement xml:lang="en">Copyright ©; 2019, Nikolov G.S., Todorova Y.D., Nikolova M.H., Emilova R.G., Hristova D.M., Kostova-Shahid P.J., Petrunov B.N.</copyright-statement><copyright-statement xml:lang="ru">Copyright ©; 2019, Николов Г.С., Тодорова Я.Д., Николова М.Х., Емилова Р.Г., Христова Д.М., Костова-Шахид П.Й., Петрунов Б.Н.</copyright-statement><copyright-year>2019</copyright-year><copyright-holder xml:lang="en">Nikolov G.S., Todorova Y.D., Nikolova M.H., Emilova R.G., Hristova D.M., Kostova-Shahid P.J., Petrunov B.N.</copyright-holder><copyright-holder xml:lang="ru">Николов Г.С., Тодорова Я.Д., Николова М.Х., Емилова Р.Г., Христова Д.М., Костова-Шахид П.Й., Петрунов Б.Н.</copyright-holder><ali:free_to_read xmlns:ali="http://www.niso.org/schemas/ali/1.0/"/><license><ali:license_ref xmlns:ali="http://www.niso.org/schemas/ali/1.0/">https://creativecommons.org/licenses/by/4.0</ali:license_ref></license></permissions><self-uri xlink:href="https://microbiol.crie.ru/jour/article/view/497">https://microbiol.crie.ru/jour/article/view/497</self-uri><abstract xml:lang="en"><p><bold>Background</bold>. It is presently known that several subsets of T-regulatory (Treg) cells, both natural and inducible maintain tolerance to environmental allergens. But the relative importance of distinct phenotypically defined Treg subsets for the clinical manifestations of IgE-mediated allergy has not been elucidated yet.</p> <p>The <bold>aim </bold>of the study was to investigate the phenotype and number of different Treg subpopulations from patients with IgE-mediated allergy compared with healthy non-allergic individuals.</p> <p><bold>Materials and methods</bold>. A group of 20 patients with clinically manifested IgE allergy and a group of 10 healthy no allergic controls were included in the study. Peripheral blood samples were taken after informed consent. Percentage and absolute count (AC) of the following regulatory subsets: naive (CD45RO-FoxP3<sup>lo</sup>), memory (RO<sup>+</sup>FoxP3<sup>+</sup>), effector (Treg eff, RO<sup>+</sup>FoxP3<sup>hi</sup>), induced (CD39<sup>+</sup>CD134<sup>+</sup>), Thl7/Treg (CD196<sup>+</sup>FoxP3<sup>+</sup>CD4Treg); Tr1 (IL-10<sup>+</sup>FoxP3<sup>-</sup>), were determined using standard 8-parameter flow cytometry (BD FACSCanto II).</p> <p><bold>Results and discussion. </bold>The share and AC of FoxP3<sup>+</sup>CD4 Treg was significantly decreased in sensitized patients as compared to controls (mean 0,6% vs. 3,3%, p&lt;0.05 and 8,7 vs. 55 cells/μl p&lt;0.001). In addition, a significantly decreased level of Tr1 cells was observed in the patients with allergy, 0,4% vs. 2,1 % in healthy controls (p&lt;0,05) as well for subset of Thl7/Treg (mean 7,7% vs. 28,4% in healthy persons, p&lt;0.01).</p> <p><bold>Conclusion. </bold>The significantly decreased number of FoxP3+CD4 Treg as well as periphery induced Tr1 and Thl7/Treg cells in patients with respiratory allergy lead to dysregulation and loss of peripheral immune tolerance, which is the pathophysiological basis for development of widely spread allergic diseases like allergic rhinitis and bronchial asthma.</p></abstract><trans-abstract xml:lang="ru"><p><bold>Актуальность. </bold>Известно, что некоторые субпопуляции Т-регуляторных клеток, наивные (nTreg) и индуцибельные (iTreg), поддерживают иммунную толерантность к аллергенам в окружающей среде. Но роль отдельных фенотипов, дефинированных субпопуляций Т-регуляторных клеток для развития IgE-обусловленной аллергии не изучена детально.</p> <p><bold>Цель </bold>– исследование фенотипа и числа разных типов Т-регуляторных клеток у пациентов с клинически выявленной IgE-обусловленной аллергией, а также установление возможных различий в количестве циркулирующих Т-регуляторных субпопуляций у пациентов по сравнению со здоровыми людьми без атопии.</p> <p><bold>Материалы и методы. </bold>В исследование были включены 20 пациентов с ингаляционной аллергией и 10 здоровых людей (контрольная группа). После получения информированного согласия у пациентов с помощью стандартной 8-параметрической проточной цитометрии (BD FACSCanto II) определены процентное соотношение и абсолютное число следующих Т-регуляторных субпопуляций: наивные (CD45ROFOXP3<sup>lo</sup>), клетки памяти (RO<sup>+</sup>FOXP3<sup>+</sup>), эффекторные (Treg eff, RO<sup>+</sup>FOXP3<sup>hi</sup>), индуцированные (CD39<sup>+</sup>CD134<sup>+</sup>), Tr1 (IL-10<sup>+</sup>FOXРЗ<sup>-</sup>) и Thl7/Treg (CD196<sup>+</sup> FOXP3<sup>+</sup> CD4Treg).</p> <p><bold>Результаты и обсуждение. </bold>У пациентов с аллергией доля и абсолютное число FOXP3<sup>+</sup>CD4 Treg значительно понижены (в среднем 0,6% против 3,3%, <italic>р</italic>&lt;0,05; и 8,7 против 55 клеток/μ1, <italic>р</italic>&lt;0,001) по сравнению с контрольной группой. Кроме того, в группе пациентов значимо снижено число индуцированных на периферии Tr1-клеток (в среднем 0,26% против 1,1% у здоровых, <italic>р</italic>&lt;0,05), как и Thl7/Treg (в среднем 7,7% против 28,4% у здоровых индивидов, <italic>р</italic>&lt;0,01).</p> <p><bold>Выводы. </bold>Уменьшение числа Т-регуляторных наивных клеток и клеток памяти, а также индуцированных на периферии Tr1- и Thl7/Treg-клеток у пациентов с клинически выявленной ингаляционной аллергией приводит к дисрегуляции иммунной системы и потере периферической толерантности, что лежит в основе развития ряда широко распространённых аллергических заболеваний, таких как аллергический ринит и астма.</p></trans-abstract><kwd-group xml:lang="en"><kwd>IgE-mediated allergy</kwd><kwd>T-regulatory cells</kwd><kwd>nTreg</kwd><kwd>Tr1 cells</kwd><kwd>Thl7/Treg</kwd></kwd-group><kwd-group xml:lang="ru"><kwd>IgE-обусловленная аллергия</kwd><kwd>Т-регуляторные клетки</kwd><kwd>nTreg</kwd><kwd>Tr1</kwd><kwd>Thl7/Treg</kwd></kwd-group><funding-group><funding-statement xml:lang="en">This study was supported by the research grant DN 13/2/14. 12. 2017 of the Bulgarian National Science Foundation</funding-statement><funding-statement xml:lang="ru">Данное исследование проведено при поддержке исследовательского гранта ДН13/2/14.12.2017 Болгарского национального научного фонда.</funding-statement></funding-group></article-meta></front><body></body><back><ref-list><ref id="B1"><label>1.</label><mixed-citation>Jutel М., Akdis С.A. 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