tibljТуберкулез и болезни легкихTuberculosis and Lung Diseases2075-12302542-1506Медицинские знания и технологии10.58838/2075-1230-2023-101-4-34-39tiblj-1742Research ArticleОРИГИНАЛЬНЫЕ СТАТЬИORIGINAL ARTICLESЗначение сигнального пути Notch в модуляции дифференцировки основных популяций Т-лимфоцитов у больных инфильтративным туберкулезом легкихSignificance of the Notch Signaling Pathway in Modulating the Differentiation of Main T-Lymphocytes Populations in Patients with Infiltrative Pulmonary TuberculosisСанинаА. Е.SaninaA. E.

Санина Алина Евгеньевна - аспирант кафедры патофизиологии.

634034, Томск, ул. Учебная, д. 39

Тел: +7 (999) 177-43-03

Anna E. Sanina - Post Graduate Student of Pathophysiology Department.

39, Uchebnaya St., Tomsk, 634034

Phone: +7 (999) 177-43-03

beresneva0307@gmail.comСеребряковаВ. А.SerebryakovaV. A.

Серебрякова Валентина Александровна - доктор медицинских наук, доцент, профессор кафедры фармакологии.

634034, Томск, ул. Учебная, д. 39

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Valentina A. Serebryakova - Doctor of Medical Sciences, Associate Professor, Professor of Pharmacology Department.

39, Uchebnaya St., Tomsk, 634034

Phone: +7 (913) 118-18-78

serebryakova-val@mail.ruУразоваО. И.UrazovaO. I.

Уразова Ольга Ивановна - доктор медицинских наук, профессор, член-корреспондент РАН, зав. кафедрой патофизиологии, профессор кафедры комплексной информационной безопасности электронно-вычислительных систем ФГБОУ ВО «ТУСУР».

634034, Томск, ул. Учебная, д. 39

Тел: +7 (903) 913-14-83

Olga I. Urazova - Doctor of Medical Sciences, Professor, Correspondent Member of RAS, Head of Pathophysiology Department, Professor of Department of Integrated Information Security of Electronic Computing System, Tomsk State University of Control Systems and Radioelectronics.

39, Uchebnaya St., Tomsk, 634034

Phone: +7 (903) 913-14-83

urazova72@yandex.ruГаджиевА. A.GadzhievA. A.

Гаджиев Алибей Агалар оглы - студент лечебного факультета.

634034, Томск, ул. Учебная, д. 39

Тел: +7 (923) 441-55-12

Alibey A. Gadzhiev - Student of General Medicine Department.

39, Uchebnaya St., Tomsk, 634034

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alibey050199@yandex.ruСтепановаЕ. П.StepanovaE. P.

Степанова Екатерина Петровна - заведующая отделением для больных туберкулезом органов дыхания.

634009, Томск, ул. Розы Люксембург, д.17

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Ekaterina P. Stepanova - Head of Respiratory Tuberculosis Department.

17, Rozy Luxemburg St., Tomsk, 634009

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stepanovaEP@stoptb.tomsk.ruКононоваТ. Е.KononovaT. E.

Кононова Татьяна Евгеньевна - кандидат медицинских наук, доцент кафедры патофизиологии.

634034, Томск, ул. Учебная, д. 39

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Tatyana E. Kononova - Candidate of Medical Sciences, Associate Professor of Pathophysiology Department.

39, Uchebnaya St., Tomsk, 634034

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kononova.te@gmail.comФГБОУ ВО «Сибирский государственный медицинский университет» МЗ РФРоссияSiberian State Medical University, Russian Ministry of HealthRussian FederationОГАУЗ «Томский фтизиопульмонологический медицинский центр» МЗ РФРоссияTomsk Phthisiopulmonology Medical Center, Russian Ministry of HealthRussian Federation20232908202310143439Copyright © Санина А.Е., Серебрякова В.А., Уразова О.И., Гаджиев А.A., Степанова Е.П., Кононова Т.Е., 20232023Санина А.Е., Серебрякова В.А., Уразова О.И., Гаджиев А.A., Степанова Е.П., Кононова Т.Е.Sanina A.E., Serebryakova V.A., Urazova O.I., Gadzhiev A.A., Stepanova E.P., Kononova T.E.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://www.tibl-journal.com/jour/article/view/1742Цель исследования

Цель исследования: оценить модулирующее влияние сигнального пути Notch на дифференцировку Th1- и Th2-лимфоцитов в условиях in vitro у больных инфильтративным туберкулезом легких.

Материалы и методы

Материалы и методы. Исследование включало 14 больных с впервые выявленным инфильтративным туберкулезом легких. Мононуклеарные лейкоциты выделяли из крови методом градиентного центрифугирования. В инкубационную среду вносили только антигены микобактерий туберкулеза в виде белка CFP10-ESAT6 или совместно с ингибитором γ-секретазы DAPT (5 мкМ/л или 10 мкМ/л). Клетки культивировали 72 ч. в полной питательной среде при 5% СО2 и 37°С. Количество Th1- и Th2-лимфоцитов определяли методом проточной цитофлуориметрии путем оценки экспрессии рецептора CD4 и внутриклеточных транскрипционных факторов T-bet и GATA-3.

Результаты

Результаты. Стимуляция клеток белком CFP10-ESAT6 сопровождалась увеличением числа Th1- и Th2-лимфоцитов только у больных с туберкулезом легких, устойчивым к изониазиду + рифампицину. Добавление в инкубационную среду DAPT в концентрации 10 мкМ/л у этих пациентов приводило к повышению количества Th1-лимфоцитов и уменьшению Th2-лимфоцитов. У больных туберкулезом легких с чувствительностью к изониазиду + рифампицину регистрировалось только снижение числа Th2-лимфоцитов. Во всех группах обследуемых подавление сигнального пути Notch приводило к повышению индекса Th1/Th2 относительно Th1/Th2 при стимуляции антигенами CFP10-ESAT6.

The objective

The objective: to evaluate the modulating effect of the Notch signaling pathway on differentiation of Th1 and Th2 lymphocytes in vitro in patients with infiltrative pulmonary tuberculosis.

Subjects and Methods

Subjects and Methods. 14 new patients with infiltrative pulmonary tuberculosis were enrolled in the study. Mononuclear leukocytes were isolated from blood by gradient centrifugation. Only Mycobacterium tuberculosis antigens in the form of the CFP10-ESAT6 protein or together with Y-secretase inhibitor DAPT (5 μМ/l or 10 μМ/l) were added to the incubation medium. Cells were cultured for 72 h in a complete nutrient medium with 5% CO2 at 37°C. Counts of Th1 and Th2 lymphocytes were determined by flow cytometry by evaluating the expression of CD4 receptor and intracellular transcription factors T-bet and GATA-3.

Results

Results. Cell stimulation with the CFP10-ESAT6 protein was accompanied by increasing number of Th1 and Th2 lymphocytes only in patients with pulmonary tuberculosis resistant to isoniazid + rifampicin. Adding DAPT at the concentration of 10 μМ/L to the incubation medium in these patients led to the growing number of Th1 lymphocytes and decrease in Th2 lymphocytes. In pulmonary tuberculosis patients who were susceptible to isoniazid + rifampicin, only decrease in the number of Th2-lymphocytes was regeistered. In all groups of subjects, suppression of the Notch signaling pathway led increase in the Th1/Th2 index versus Th1/Th2 stimulated with CFP10-ESAT6 antigens.

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The authors declare that there are no conflicts of interest present.