Т-ХЕЛПЕРЫ И ИХ КЛЕТКИ-МИШЕНИ ПРИ COVID-19

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Инфекция и иммунитет. 2021;

Т-ХЕЛПЕРЫ И ИХ КЛЕТКИ-МИШЕНИ ПРИ COVID-19

Кудрявцев И. В., Головкин А. С., Тотолян А. А.

https://doi.org/10.15789/2220-7619-THC-1882

Аннотация

Данный обзор посвящен анализу субпопуляционного состава и фенотипическим изменениям, которые были отмечены для различных субпопуляций Т-хелперов (Th) периферической крови и их клеток-мишеней у пациентов с острой инфекцией, вызванной SARS-CoV-2. Уже в первых работах, посвященных анализу фенотипа и функциональных характеристик дендритных клеток, отмечалось снижение ключевых молекул, отвечающих за презентацию антигенов (HLA-DR), миграцию в лимфоидную ткань (CCR7) и формирование костимуляционного сигнала (CD80 и CD86). Некоторыми исследователями показано, что SARS-CoV-2-специфические Т-хелперы появлялись в циркуляцию уже на 2-4 день после появления первых симптомов, а позднее формирование клонов SARS-CoV-2-специфических Th было связано с неблагоприятным исходом COVID-19. В острой фазе инфекции уровень Th1 клеток изменялся слабо, тогда как среди их основных клеток-мишеней – CD8+ Т-лимфоцитов и НК-клеток – в периферической крови преобладали клетки эффекторных популяций с высокой экспрессией маркеров клеточного «старения» (TIM3, PD-1, BTLA, TIGIT и т.д.), а уровень макрофагов жидкости бронхо-альвеолярного лаважа (ЖБАЛ) повышался. При анализе клеток, участвующих в запуске воспаления по 2 типу, большинством исследователей отмечалось увеличение доли CD4+ Т-клеток, обладавших фенотипом и свойства Th2. Более того, снижение в периферической крови основных клеток-мишеней Th2 – базофилов и эозинофилов – было тесно связано с тяжелым течением COVID-19, тогда как в легочной ткани наблюдалось увеличение уровня тучных клеток и активности медиаторов, высвобождавшихся в ходе их дегрануляции. Содержание Th17 в периферической крови могло быть тесно связано с тяжестью течения COVID-19 – минимальные значения этих клеток были характерны для тяжелых форм заболевания, тогда как в составе ЖБАЛ доля Th17 и концентрации секретируемых ими цитокинов резко возрастала. Увеличение в циркуляции нейтрофилов было тесно связано с тяжесть COVID-19, тогда как в рамках общего пула этих клеток возрастала доля незрелых клеток с пониженной способностью к продукции активных форм кислорода. В большинстве работ отмечалось снижение уровня общего уровня Tfh клеток в циркулирующей крови, тогда как в рамках Tfh увеличивалась доля активированных клеток и отмечалось нарушение баланса между «регуляторными» Tfh1 и «провоспалительными» Th2 и Th17. У пациентов с острым COVID-19 в циркуляции были снижены практически все основные субпопуляции «наивных» В-клеток и В-клеток памяти, но отмечалось увеличение доли эффекторных клеток – циркулирующих предшественников плазматических клеток с фенотипом CD27hiCD38hiCD24−, а также функционально неактивных CD21low В-лимфоцитов. Анализ данных литературы указывает на наличие существенных нарушений в функционировании всех основных субпопуляций Th и их клеток-мишеней в острую фазу COVID-19, которые могут сохраняться после элиминации патогена и являться одной из причин проявления «пост-ковидных» нарушений.

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Russian Journal of Infection and Immunity. 2021;

T HELPER CELL SUBSETS AND THEIR TARGET CELLS IN ACUTE COVID-19

Kudryavtsev I. , Golovkin A. , Totolian A.

https://doi.org/10.15789/2220-7619-THC-1882

Abstract

Current review presents a brief overview of the immune system dysregulation during acute COVID-19 and illustrates the main alterations in peripheral blood CD4+ T-cell (Th) subsets and their target cells. Dendritic cell dysfunction effects induced by SARS-CoV-2 exhibited decreased expression of cell-surface HLA-DR, CCR7 and co-stimulatory molecules CD80 and CD86, indicating a reduction of antigen presenting, migrating and activation capacities of peripheral blood dendritic cells. SARS-CoV-2-specific Th cells could be detected as early as days 2–4 post-symptom onset, while the extended absence of SARS-CoV-2-specific Th cells was associated with severe and/or poor COVID-19 outcome. Firstly, in acute COVID-19 the frequency of Th1 cell was comparable with control levels, but several studies have reported an upregulation of inhibitory immune checkpoint receptors and exhaustion-associated molecules (TIM3, PD-1, BTLA, TIGIT etc.) on circulating CD8+ T-cells and NK-cell, while the level of macrophage was increased in bronchoalveolar lavage (BAL) samples. Next, type 2 immune responses are mediated mainly by Th2 cells, and several studies have revealed a skewing towards Th2 in peripheral blood samples from patients with acute COVID-19. Furthermore, the decreases of circulating main Th2 target cells – basophiles and eosinophils – were associated with severe COVID-19, while the lung tissue was enriched with mast cells and their mediators, that were realized during degranulation. Moreover, the frequencies of peripheral blood Th17 cell were closely linked with COVID-19 severity, thus, low levels of Th17 cell were observed in patients with severe COVID-19, but in BAL the relative numbers of Th17 cell as well as the concentrations of their effector cytokines were dramatically increased. It was shown that severe COVID-19 patients had higher relative numbers of neutrophils if compared with healthy controls, and the majority of patients with COVID-19 had increased frequencies and absolute numbers of immature neutrophils with altered ROS production. Finally, the frequencies of Tfh cells was decreased during acute COVID-19 infection. Elevated numbers of activated Tfh were found as well as the alterations in Tfh cell subsets characterized by the decrease of ‘regulatory’ Tfh1 cell and increase of ‘pro-inflammatory’ Tfh2 and Tfh17 cell subsets were revealed. Descriptions of peripheral blood B cells during an acute SARS-CoV-2 infection had reported the relative B cell lymphopenia with the decreased frequencies of ‘naïve’ and memory B cell subsets, as well as increased levels of CD27hiCD38hiCD24− plasma cell precursors and atypical CD21low B cells. Thus, the emerging evidences indicate that functional alterations occur in all Th cell subsets, and they are linked with loss-of-functions of main Th cell subsets target cells. Furthermore, recovered individuals could suffer from long-term immune responses dysregulation and other persistent symptoms for many months even after SARS-CoV-2 elimination, a condition referred to as post-acute COVID-19 syndrome.

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