ssmuБюллетень сибирской медициныBulletin of Siberian Medicine1682-03631819-3684Siberian State Medical University, the Ministry of Healthcare of the Russian Federation10.20538/1682-0363-2019-1-286-293ssmu-2195Research ArticleОРИГИНАЛЬНЫЕ СТАТЬИORIGINAL PAPERSВлияние гуморальных факторов гомеостатической пролиферации на T-регуляторные клетки in vitroThe influence of humoral factors of homeostatistic proliferation on t-regulatory cells in vitroШевыревД. В.ShevyrevD. V.

Шевырев Даниил Вадимович, аспирант, лаборатория клинической иммунопатологии

630099, г. Новосибирск, ул. Ядринцевская, 14

Shevyrev Daniil V., PhD Student, Laboratory of Clinical Immunopathology

14, Yadrintsevskaya Str., Novosibirsk, 630099

dr.daniil25@mail.ruhttps://orcid.org/0000-0003-3327-3630БлиноваЕ. А.BlinovaE. A.

Блинова Елена Андреевна, кандидат биологических наук, старший научный сотрудник, лаборатория клинической иммунопатологии

630099, г. Новосибирск, ул. Ядринцевская, 14

Blinova Elena A., PhD, Senior Researcher, Laboratory of Clinical Immunopathology

14, Yadrintsevskaya Str., Novosibirsk, 630099

https://orcid.org/0000-0002-1756-1782КозловВ. А.KozlovV. A.

Козлов Владимир Александрович, доктор медицинских наук, профессор, академик РАН, заведующий лабораторией клинической иммунопатологии, НИИФКИ

630099, г. Новосибирск, ул. Ядринцевская, 14

Kozlov Vladimir A., DM, Professor, Аcademician of RAS, Scientific Supervisor of RIFCI, Head of the Laboratory of Clinical Immunopathology, RIFCI

14, Yadrintsevskaya Str., Novosibirsk, 630099

Научно-исследовательский институт фундаментальной и клинической иммунологии (НИИ ФКИ)РоссияResearch Institute of Fundamental and Clinical Immunology (RIFCI)Russian Federation201916052019181286293Copyright © Шевырев Д.В., Блинова Е.А., Козлов В.А., 20192019Шевырев Д.В., Блинова Е.А., Козлов В.А.Shevyrev D.V., Blinova E.A., Kozlov V.A.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://bulletin.ssmu.ru/jour/article/view/2195

Цель – изучение влияния гуморальных факторов гомеостатической пролиферации интерлейкина (IL) 7 и IL-15 на фенотипические и функциональные характеристики T-регуляторных клеток у здоровых доноров in vitro.

Материалы и методы

Материалы и методы. В исследование были включены 15 условно здоровых доноров. Методом проточной цитометрии проводились фенотипирование, оценка экспрессии FoxP3 и основных функциональных молекул T-регуляторных клеток (CTLA-4, PD-L1, HLA-D) до и после культивирования с IL-7 и IL-15, а также с анти-CD3-антителами в комбинации с IL-2. Оценивался пролиферативный ответ T-регуляторных клеток на стимуляцию указанными факторами.

Результаты

Результаты. Обнаружено, что факторы гомеостатической пролиферации способствуют сохранению фенотипа CD4+CD25+FoxP3+ и численному поддержанию T-регуляторных лимфоцитов в культуре, а также могут положительно влиять на экспрессию таких функциональных молекул, как PD-L1 и HLA-DR. Кроме того показано, что указанные факторы способны вызывать пролиферацию T-регуляторных клеток в существенно более низкой степени, чем CD4+-лимфоцитов.

Заключение

Заключение. Выявлена способность гомеостатических факторов IL-7 и IL-15 поддерживать фенотип T-регуляторных клеток и экспрессию функциональных маркеров. По-видимому, это играет важную роль в условиях лимфопении при снижении числа эффекторных лимфоцитов – основных продуцентов IL-2, которому отводится первостепенная роль в гомеостазе T-регуляторных клеток в норме.

Aim

Aim. The aim of this study was the investigation of the influence of humoral factors of homeostatic proliferation IL-7 and IL-15 on T-regulatory cells in healthy donors.

Materials and methods

Materials and methods. The study included 15 conditionally healthy donors. Phenotyping and evaluation of expression changes of transcription factor FoxP3 and the main functional molecules on T-regulatory cells such as PD-L1, CTLA-4 and HLA-DR during cultivation under IL-7, IL-15 and anti-CD3 stimulation combined with IL-2 were performed by flow cytometry. Also, we estimated proliferation intensity of T-regulatory cells in the course of cultivation.

Results

Results. We revealed that humoral factors of homeostatic proliferation can effectively support a pool of T-regulatory cells during cultivation by number and phenotype and can maintain expression of important molecules such as PD-L1 and HLA-DR on regulatory T-cell surface. In addition, our study showed that IL-7 and IL-15 can cause relatively low T-regulatory cells proliferation in comparison to CD4+- lymphocytes.

Conclusion

Conclusion. The observed ability of homeostatic proliferation factors to maintain T-regulatory cells pool presumably can play an important role in lymphopenic conditions when the number of effector cells is decreased and the insufficiency of interleukin IL-2 is observed, which plays a primary role in the homeostasis of T-regulatory cells in normal conditions.

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