mimmunМедицинская иммунологияMedical Immunology (Russia)1563-06252313-741XSPb RAACI10.15789/1563-0625-2009-2-3-245-254mimmun-311Research ArticleОРИГИНАЛЬНЫЕ СТАТЬИORIGINAL ARTICLESДЕФЕКТ АНТИГЕНПРЕЗЕНТИРУЮЩИХ КЛЕТОК У БОЛЬНЫХ ТУБЕРКУЛЕЗОМ ЛЕГКИХA DEFICIENCY OF ANTIGEN-PRESENTING CELLS IN PATIENTS WITH PULMONARY TUBERCULOSISСахноЛ. В.SakhnoL. V.

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ct_lab@mail.ruРаспайЖ. М.RaspayZh. M.ct_lab@mail.ruТихоноваМ. А.TikhonovaM. A.ct_lab@mail.ruНиконовС. Д.NiconovS. D.ct_lab@mail.ruЖдановО. А.ZhdanovO. A.ct_lab@mail.ruОстанинА. А.OstaninA. A.ct_lab@mail.ruЧерныхЕ. Р.ChernykhE. R.ct_lab@mail.ruГУ НИИ клинической иммунологии СО РАМН, г. НовосибирскРоссияОГУЗ Новосибирская клиническая туберкулезная больница № 1, г. НовосибирскРоссия200919072014112-3245254Copyright © Сахно Л.В., Распай Ж.М., Тихонова М.А., Никонов С.Д., Жданов О.А., Останин А.А., Черных Е.Р., 20142014Сахно Л.В., Распай Ж.М., Тихонова М.А., Никонов С.Д., Жданов О.А., Останин А.А., Черных Е.Р.Sakhno L.V., Raspay Z.M., Tikhonova M.A., Niconov S.D., Zhdanov O.A., Ostanin A.A., Chernykh E.R.This work is licensed under a Creative Commons Attribution 4.0 License.https://www.mimmun.ru/mimmun/article/view/311

Резюме. В работе были исследованы фенотипические и функциональные свойства антигенпрезентирующих клеток (АПК: моноцитов крови и генерированных in vitro макрофагов / дендритных клеток) у больных туберкулезом легких (ТБ, n = 192), различающихся по уровню пролиферативного ответа на антигены M. tuberculosis (PPD-отвечающие и PPD-анергичные пациенты, n = 118 и 74 соответственно). Установлено, что у больных ТБ изменены все три типа АПК. На уровне моноцитов это проявляется снижением экспрессии CD86 и HLA-DR молекул, 2-кратным увеличением субпопуляции CD14+CD16+ клеток, FasL+ и IL-10+ моноцитов, а также повышенной продукцией IL-10 и IL-6 в ответ на стимуляцию эндотоксином. На уровне макрофагов регистрируется дисбаланс продукции Th1/Th2-цитокинов (снижение продукции IFNγ и IL-18 в сочетании с усилением продукции IL-6 и IL - 10), а также снижение аллостимуляторной активности в смешанной культуре лимфоцитов. На уровне дендритных клеток это проявляется снижением количества зрелых активированных CD25+ клеток, дефицитом продукции IFNγ в сочетании с повышенной способностью секретировать IL-10 и IL-6 и нарушением функциональной (аллостимуляторной) активности. При этом наиболее выраженные изменения свойств различных типов АПК регистрируются в подгруппе больных ТБ со сниженным пролиферативным ответом на PPD. Обсуждается возможная роль дисфункций АПК в нарушении антигенспецифического ответа при туберкулезной инфекции.

Abstract. The phenotype and functional properties of antigen-presenting cells (APCs: blood monocytes and in vitro generated macrophages/dendritic cells) were investigated in patients with pulmonary tuberculosis (TB, n = 192) with different levels of proliferative response to M. tuberculosis antigens (PPD-responsive vs PPD - anergic patients, n = 118 and 74, respectively). A functional deficiency of all 3 types of APCs was revealed in patients with TB. I.e., a monocyte disfunction was displayed by low CD86 and HLA-DR expression, 2-fold increase of CD14+CD16+ subset, high level of FasL+ and IL-10+ cells, and enhanced IL-10 and IL-6 production upon LPS-stimulation. The in vitro generated macrophages from blood monocytes challenged with GM-CSF, were characterized by shifted Th1/Th2 balance (down-regulated production of IFNγ and IL-18 combined with up-regulation of IL-6 and IL-10), and reduced allostimulatory activity in mixed lymphocyte culture. The dendritic cells were characterized by decrease of mature, activated CD25+ cells, low level of IFNγ production in conjunction with enhanced capacity to produce IL - 10 and IL-6, and profound reduction of functional (allostimulatory) activity. The APC disfunction of were most prominent in PPD-anergic patients. A possible role of APC disfunctions in disturbed antigen-specific T-cell response to M. tuberculosis is discussed.

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