mimmunМедицинская иммунологияMedical Immunology (Russia)1563-06252313-741XSPb RAACI10.15789/1563-0625-AIP-3222mimmun-3222Research ArticleОРИГИНАЛЬНЫЕ СТАТЬИORIGINAL ARTICLESИзменения субпопуляционного состава CD8+Т-лимфоцитов в периферической крови пациентов с хроническим саркоидозом легкихAlterations in peripheral blood CD8+T cell subsets in patients with lung sarcoidosisРубинштейнА. А.RubinsteinA. A.

младший научный сотрудник лаборатории клеточной иммунологии 

Junior Researcher, Laboratory of Cellular Immunology

arrubin6@mail.ruКудрявцевИ. В.KudryavtsevI. V.

к.б.н., заведующий лабораторией клеточной иммунологии; доцент кафедры иммунологии

PhD (Biology), Head, Laboratory of Cellular Immunology

igorek1981@yandex.ruЛазареваН. М.LazarevaN. M.

к.м.н., заведующая лабораторией молекулярно-генетических исследований клиники, врач клинической лабораторной диагностики 

PhD (Medicine), Head, Clinic’s Molecular Genetic Research Laboratory, Clinical Laboratory Diagnostics Physician

nmlazareva@gmail.comАкишеваТ. В.AkishevaT. V.

младший научный сотрудник лаборатории клеточной иммунологии 

Junior Researcher, Laboratory of Cellular Immunology

akisheva@yandex.ruБарановаО. П.BaranovaO. P.

к.м.н., старший научный сотрудник Научно-исследовательского института интерстициальных и орфанных заболеваний легких, доцент кафедры пульмонологии 

PhD (Medicine), Senior Researcher of the Research Institute of Interstitial and Orphan Diseases, Associate Professor, Department of Pulmonology

dr_baranova@mail.ruСесьТ. П.Ses’T. P.

д.б.н., профессор, профессор кафедры иммунологии 

MD, PhD (Biology), Professor, Department of Immunology

sestp@mail.ruИльковичМ. М.IlkovichM. M.

д.м.н., профессор, директор Научно- исследовательского института интерстициальных и орфанных заболеваний легких, заведующий кафедрой пульмонологии 

PhD, MD (Medicine), Professor, Director of the Research Institute of Interstitial and Orphan Diseases, Head of the Department of Pulmonology

mihilkovich@yanbex.ruТотолянАрег А.TotolianAreg A.

д.м.н., профессор, академик РАН, заведующий лабораторией молекулярной иммунологии, директор ФБУН «Санкт-Петербургский научно-исследовательский институт эпидемиологии и микробиологии имени Пастера» Федеральной службы по надзору в сфере защиты прав потребителей и благополучия человека; заведующий кафедрой иммунологии

PhD, MD (Medicine), Professor, Full Member, Russian Academy of Sciences, Head, Laboratory of Molecular Immunology, Director, Saint Petersburg Pasteur Institute; Head, Department of Immunology, First St. Petersburg State I. Pavlov Medical University

totolian@pasteurorg.ruФГБНУ «Институт экспериментальной медицины»РоссияInstitute of Experimental MedicineRussian FederationФГБНУ «Институт экспериментальной медицины»; ФГБОУ ВО «Первый Санкт-Петербургский государственный медицинский университет имени академика И.П. Павлова» Министерства здравоохранения РФРоссияInstitute of Experimental Medicine; First St. Petersburg State I. Pavlov Medical UniversityRussian FederationФГБУ «Российский научно-исследовательский институт гематологии и трансфузиологии Федерального медико-биологического агентства»РоссияRussian Research Institute of Hematology and Transfusiology, Federal Medical-Biological AgencyRussian FederationФГБОУ ВО «Первый Санкт-Петербургский государственный медицинский университет имени академика И.П. Павлова» Министерства здравоохранения РФРоссияFirst St. Petersburg State I. Pavlov Medical UniversityRussian FederationФГБОУ ВО «Первый Санкт-Петербургский государственный медицинский университет имени академика И.П. Павлова» Министерства здравоохранения РФ; ФБУН «Санкт-Петербургский научно-исследовательский институт эпидемиологии и микробиологии имени Пастера» Федеральной службы по надзору в сфере защиты прав потребителей и благополучия человекаРоссияFirst St. Petersburg State I. Pavlov Medical University; Saint Petersburg Pasteur InstituteRussian Federation20252012202527613231338Copyright © Рубинштейн А.А., Кудрявцев И.В., Лазарева Н.М., Акишева Т.В., Баранова О.П., Сесь Т.П., Илькович М.М., Тотолян А.А., 20252025Рубинштейн А.А., Кудрявцев И.В., Лазарева Н.М., Акишева Т.В., Баранова О.П., Сесь Т.П., Илькович М.М., Тотолян А.А.Rubinstein A.A., Kudryavtsev I.V., Lazareva N.M., Akisheva T.V., Baranova O.P., Ses’ T.P., Ilkovich M.M., Totolian A.A.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://www.mimmun.ru/mimmun/article/view/3222

Саркоидоз – это системное иммунноопосредованное гранулематозное заболевание неизвестной по настоящее время этиологии, характеризующееся инфильтрацией тканей макрофагами и лимфоцитами, включая CD8+Т-лимфоциты, и сопутствующим образованием неказеозных гранулем. Целью исследования являлось изучение различных субпопуляций CD8+Т-клеток в периферической крови больных хроническим течением саркоидоза органов дыхания с применением маркеров созревания, «поляризации», дифференцировки и миграции Т-лимфоцитов. Образцы периферической венозной крови были получены от 34 пациентов с впервые выявленным хроническим саркоидозом органов дыхания на фоне естественного течения без применения иммуносупрессивной терапии. Диагноз «саркоидоз» был установлен на основе комплексного клинико-лучевого исследования и подтвержден гистологически у 94,12% пациентов. В качестве контрольной группы использовалась периферическая венозная кровь условно здоровых доноров (n = 40), сопоставимых по полу и возрасту с пациентами с легочным саркоидозом. С применением многоцветной проточной цитометрии было показано, что саркоидозе снижалось как относительное, так и абсолютное содержание CD45RA+CD62L+«наивных» CD8+Т-клеток и CD45RA-CD62L+CD8+Т-клеток центральной памяти относительно значений контрольной группы, а также ЕМ1-клеток (CD45RA-CD62L-CD27+CD28+) и преэффекторов 1-го типа (CD45RA+CD62L-CD27+CD28+). В ходе последующих исследований по экспрессии CXCR3 и CCR6 CD8+Т-клеток были разделены на Tc1 (CCR6-CXCR3+), Tc2 (CCR6-CXCR3-), Tc17 (CCR6+CXCR3-) и «дважды позитивные» Tc17.1 (CCR6+CXCR3+). В случае субпопуляций CD8+Т-клеток, способных к экспрессии CXCR3 (Tc1 и Tc17.1), нами были отмечены достоверные снижения как относительного, так и абсолютного содержания этих клеток у пациентов с саркоидозом относительно значений условно здорового контроля. На фоне снижения Tc1-клеток нами было отмечено увеличение доли Тс2-клеток в периферической крови пациентов с саркоидозом. Более того, при саркоидозе относительное содержание Tc1-клеток находилось в обратной зависимости от уровня АПФ в сыворотке крови (r = -0,456 при р = 0,010), а по мере роста АПФ в сыворотке крови больных отмечалось повышение доли Тс2-клеток (r = 0,623 при р < 0,001). Таким образом, полученные нами результаты указывают на то, что CD8+Т-лимфоциты могут играть роль в патогенеза саркоидоза. Для дальнейшей систематизации полученных данных требуются более расширенные клинико-иммунологические сопоставления.

Sarcoidosis is a systemic inflammatory disorder of unknown etiology characterized by tissue infiltration with macrophages and lymphocytes, including CD8+T cells, and associated non-caseous granuloma formation. The aim of the study was to investigate various peripheral blood CD8+T cells from patients with chronic respiratory sarcoidosis using markers of T cell maturation and ‘polarization’. Peripheral blood samples were collected from 34 patients with newly diagnosed chronic sarcoidosis of respiratory organs with the background of a natural course of disease, and without a history of immunosuppressive therapy. The diagnosis of pulmonary sarcoidosis was performed according to the standard criteria and was confirmed by histological examination for 94.1% of patients. Peripheral venous blood samples from healthy, gender- and age-matched volunteers (n = 40), were used as control specimens. Multicolor flow cytometry revealed that patients with sarcoidosis had decreased levels of CD45RA+CD62L+ ‘naïve’ and CD45RA-CD62L+ central memory CD8+T cells as compared with healthy controls. Moreover, the frequencies of ЕМ1 (CD45RA-CD62L-CD27+CD28+) and pre-effector type 1 (CD45RA+CD62L-CD27+CD28+) cells were also reduced. In order to assess the relevant ‘polarized’ CD8+T cell subsets, we have specified the Tc1 (CCR6-CXCR3+), Tc2 (CCR6-CXCR3-), Tc17 (CCR6+CXCR3-), and double-positive Tc17.1 (CCR6+CXCR3+) cell populations. The relative and absolute numbers of CXCR3-expressing CD8+T cell subsets (Tc1 and Tc17.1 were found to be significantly decreased in patients with sarcoidosis if compared to healthy controls. By contrary, Тс2 CD8+T cell contents were significantly elevated. Furthermore, the relative numbers of Tc1 cells negatively correlated with serum ACE levels (r = -0.456; р = 0.01), whereas Тс2 levels positively correlated with serum ACE levels (r = 0.623; р < 0.001). Thus, our results indicate that CD8+T cells may play a role in pathogenesis of sarcoidosis. More extensive clinical and immunological comparisons are required for further systematization of the obtained data.

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