rspНаучно-практическая ревматологияRheumatology Science and Practice1995-44841995-4492IMA-PRESS, LLC10.14412/1995-4484-2016-442-455rsp-2275Research ArticleПРОГРЕСС В РЕВМАТОЛОГИИ В XXI ВЕКЕPROGRESS IN RHEUMATOLOGY IN THE XXI CENTURYКлинико-патогенетическое значение Foxр3+ регуляторных Т-клеток при ревматоидном артритеThe clinical and pathogenetic value of Foxp3+ T regulatory cells in rheumatoid arthritisАвдееваА. С.AvdeevaA. S.

лабораториz иммунологии и молекулярной биологии ревматических заболеваний

научный сотрудник 

115522 Москва, Каширское шоссе, 34А

34A, Kashirskoe Shosse, Moscow 115522

9056249400@mail.ruРубцовЮ. П.RubtsovYu. P.

факультет фундаментальной медицины

кафедра биохимии и молекулярной медицины

доцент

119192 Москва, Ломоносовский проспект, 31, корп. 5

Faculty of Fundamental Medicine 

Department of Biochemistry and Molecular Medicine

31, Lomonosovsky Prospect, Build. 5, Moscow 119192

 

ДыйкановД. Т.DyikanovD. T.

факультет фундаментальной медицины

кафедра биохимии и молекулярной медицины

аспирант

119192 Москва, Ломоносовский проспект, 31, корп. 5

Faculty of Fundamental Medicine 

Department of Biochemistry and Molecular Medicine

31, Lomonosovsky Prospect, Build. 5, Moscow 119192

НасоновЕ. Л.NasonovE. L.

115522 Москва, Каширское шоссе, 34А

кафедра ревматологии, Институт профессионального образования

зав. кафедрой

119991 Москва, ул. Трубецкая, 8, стр. 2 

34A, Kashirskoe Shosse, Moscow 115522

Department of Rheumatology, Institute of Professional Education

8, Trubetskaya St., Build. 2, Moscow 119991 

ФГБНУ Научно-исследовательский институт ревматологии им. В.А. Насоновой, МоскваРоссияV.A. Nasonova Research Institute of Rheumatology, MoscowRussian FederationФГБОУ ВО «Московский государственный университет им. М.В. Ломоносова»РоссияM.V. Lomonosov Moscow State UniversityRussian FederationФГБНУ Научно-исследовательский институт ревматологии им. В.А. Насоновой, Москва; ФГБОУ ВО «Первый Московский государственный медицинский университет им. И.М. Сеченова» Минздрава России, МоскваРоссияV.A. Nasonova Research Institute of Rheumatology, Moscow; I.M. Sechenov First Moscow State Medical University, Ministry of Health of Russia, MoscowRussian Federation201620102016544442455Copyright © Авдеева А.С., Рубцов Ю.П., Дыйканов Д.Т., Насонов Е.Л., 20162016Авдеева А.С., Рубцов Ю.П., Дыйканов Д.Т., Насонов Е.Л.Avdeeva A.S., Rubtsov Y.P., Dyikanov D.T., Nasonov E.L.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://rsp.mediar-press.net/rsp/article/view/2275

Регуляторные Т-клетки (Трег) играют ключевую роль в иммунной системе благодаря подавлению гипериммунного ответа в отношении аутоантигенов, а также кишечных условно-патогенных микроорганизмов. В последние годы получены данные о способности Трег подавлять различные иммуновоспалительные реакции в ответ на широкий спектр физиологических и патологических стимулов, включая микроорганизмы, опухолевые клетки, аллогенные трансплантаты, клетки плода.

Трег экспрессируют широкий спектр мембранных молекул, которые определяют их функциональную активность и дают возможность идентифицировать эти клетки, однако до сих пор не обнаружен универсальный поверхностный маркер, который позволил бы выделить данную клеточную субпопуляцию из пула Т-лимфоцитов. Наиболее специфическим внутриклеточным маркером Трег является ядерный фактор транскрипции Foxp3, который имеет фундаментальное значение в развитии Трег и их ингибиторной функции.

Результаты подавляющего большинства исследований указывают на увеличение содержания Трег в синовиальной жидкости пациентов с ревматоидным артритом (РА), однако данные об уровне данной клеточной субпопуляции в периферической крови весьма противоречивы. Большинство исследователей наблюдали уменьшение процентного содержания циркулирующих Трег, в то время как в других работах выявлено его увеличение или отсутствие отличий от соответствующего показателя здоровых доноров или пациентов с ос- теоартрозом. Полагают, что количественный дефект CD4+CD25+Foxp3+CD127-регуляторных клеток особенно характерен для раннего РА и ассоциируется с риском развития последнего у бессимптомных пациентов, позитивных по антителам к циклическому цитруллинированному пептиду. Применение базисных и генно-инженерных биологических препаратов сопровождается определенным изменением уровня и функциональной активности Трег, с чем в ряде случаев связывают лечебный эффект препаратов.

Таким образом, Трег в настоящее время отводят важную роль в патогенезе аутоиммунных ревматических заболеваний, в частности, РА. Снижение уровня и функциональной активности Трег, вероятно, лежит в основе развития неконтролируемого хронического воспаления, приводящего к множественным органным повреждениям. 

T regulatory cells (Tregs) play a key role in the immune system due to the suppression of a hyperimmune response to autoantigens and opportunistic enteric microorganisms. In recent years, there has been evidence that Tregs can suppress various immunoinflammatory responses to a wide range of physiological and pathological stimuli, including microorganisms, tumor cells, allogeneic grafts, and fetal cells.

Tregs express a broad spectrum of membrane molecules that determine their functional activity and make it possible to identify these cells; however, none has discovered a universal surface marker that would distinguish this cell subpopulation from a pool of T lymphocytes. The most specific intracellular marker for Tregs is the nuclear transcription factor Foxp3 that is of fundamental importance in the development of Tregs and their inhibitory function.

The results of the vast majority of studies indicate that there are increased numbers of Tregs in the synovial fluid of patients with rheumatoid arthritis (RA); however, the data on the level of this cell population in their peripheral blood are very contradictory. The majority of investigators have observed a decrease in the percentage of circulating Tregs while other studies have revealed its increase or no differences from the corresponding value of healthy donors or patients with osteoarthritis. It is believed that a quantitative defect in CD4+CD25+Foxp3+CD127 regulatory cells is especially characteristic of early RA and associated with the risk of the latter in asymptomatic patients positive for anti-cyclic citrullinated peptide antibodies. The use of disease-modifying antirheumatic drugs and biologic agents is accompanied by a certain change in the level and functional activity of Tregs, which is responsible for the therapeutic effect of the medicaments.

Thus, an important part is assigned to Tregs in the pathogenesis of autoimmune rheumatic diseases, RA in particular. The decrease in the level and functional activity of Tregs is likely to underlie the development of uncontrolled chronic inflammation leading to multiple organ damages. 

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