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Медицинская иммунология

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ИММУНОБИОЛОГИЯ ОСТРОЙ РЕАКЦИИ «ТРАНСПЛАНТАТ ПРОТИВ ХОЗЯИНА»

https://doi.org/10.15789/1563-0625-2015-6-499-516

Аннотация

Для целого ряда заболеваний системы кроветворения единственным методом излечения является аллогенная трансплантация гемопоэтических стволовых клеток, которая имеет своей целью замену кроветворной системы реципиента на донорскую. Однако попадание в организм реципиента содержащихся в трансплантате зрелых Т-лимфоцитов может приводить к развитию тяжелого пост-трансплантационного осложнения – реакции «трансплантат против хозяина» (РТПХ). Она вызвана тем, что иммунная система донора содержит клоны Т-лимфоцитов, специфичные к аллоантигенам реципиента, которые, встречая свои антигены, активируются и вызывают системное повреждение здоровых тканей. Наличие аллореактивных клонов обусловлено генетическими различиями между донором и реципиентом. Важнейшим фактором, определяющим успех трансплантации, является совместимость по генам главного комплекса гистосовместимости, которые экспрессируются во всех ядерных клетках и отвечают за презентацию антигенов клеткам иммунной системы. В настоящее время созданы обширные банки доноров стволовых гемопоэтических клеток, которые позволяют подобрать для большинства пациентов совместимого донора. Однако это не полностью предотвращает развитие РПТХ, так как помимо генов главного комплекса гистосовместимости, донор и реципиент могут различаться по так называемым минорным антигенам совместимости. Минорные антигены обусловлены генетическими полиморфизмами во всех кодирующих областях генома. Дополнительным фактором, способствующим развитию реакции «трансплантат против хозяина», является предтрансплантационная подготовка пациента, которая необходима для приживления трансплантата, но в качестве побочного эффекта приводит к формированию в организме реципиента провоспалительного окружения. Тяжелые формы РТПХ развиваются приблизительно у 40% пациентов, совпадающих по генам главного комплекса гистосовместимости, а в случаях неполной совместимости эта доля еще больше. Смертность от РТПХ сравнима с другими причинами посттрансплантационной летальности, такими как рецидив изначального заболевания и вирусные инфекции. Таким образом, развитие тяжелых форм РТПХ существенно лимитирует клиническое применение трансплантации стволовых кроветворных клеток. Агрессивная иммуносупрессия или исключение из трансплантата донора зрелых Т-лимфоцитов приводит к увеличению вероятности рецидива и ослабляет противоинфекционный иммунитет, что требует поиска альтернативных, более специфичных путей профилактики реакции «трансплантат против хозяина». В настоящем обзоре будут рассмотрены механизмы формирования аллореактивных клонов Т-лимфоцитов и этапы патогенеза острой формы реакции «трансплантат против хозяина».

Об авторах

Г. А. Ефимов
ФГБУ «Гематологический научный центр» Министерства здравоохранения РФ, Москва, Россия
Россия

к.б.н., заведующий лабораторией трансплантационной иммунологии ФГБУ «Гематологический научный центр» Министерства здравоохранения РФ, Москва, Россия 125167, Россия, Москва, Новый Зыковский пр., 4. Тел.: 8 (964) 551-55-51



А. С. Вдовин
ФГБУ «Гематологический научный центр» Министерства здравоохранения РФ, Москва, Россия
Россия

научный сотрудник лаборатории трансплантационной иммунологии ФГБУ «Гематологический научный центр» Министерства здравоохранения РФ, Москва, Россия



А. А. Григорьев
ФГБУ «Гематологический научный центр» Министерства здравоохранения РФ, Москва, Россия
Россия

к.б.н, научный сотрудник лаборатории трансплантационной иммунологии ФГБУ «Гематологический научный центр» Министерства здравоохранения РФ, Москва, Россия



С. Ю. Филькин
ФГБУ «Гематологический научный центр» Министерства здравоохранения РФ, Москва, Россия
Россия

научный сотрудник лаборатории трансплантационной иммунологии ФГБУ «Гематологический научный центр» Министерства здравоохранения РФ, Москва, Россия



Н. А. Быкова
ФГБУ «Гематологический научный центр» Министерства здравоохранения РФ, Москва, Россия
Россия

научный сотрудник лаборатории трансплантационной иммунологии ФГБУ «Гематологический научный центр» Министерства здравоохранения РФ, Москва, Россия



В. Г. Савченко
ФГБУ «Гематологический научный центр» Министерства здравоохранения РФ, Москва, Россия
Россия

д.м.н., профессор, академик РАН, генеральный директор ФГБУ «Гематологический научный центр» Министерства здравоохранения РФ, Москва, Россия



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Для цитирования:


Ефимов Г.А., Вдовин А.С., Григорьев А.А., Филькин С.Ю., Быкова Н.А., Савченко В.Г. ИММУНОБИОЛОГИЯ ОСТРОЙ РЕАКЦИИ «ТРАНСПЛАНТАТ ПРОТИВ ХОЗЯИНА». Медицинская иммунология. 2015;17(6):499-516. https://doi.org/10.15789/1563-0625-2015-6-499-516

For citation:


Efimov G.A., Vdovin A.S., Grigoryev A.A., Filkin S.Yu., Bykova N.A., Savchenko V.G. IMMUNOBIOLOGY OF ACUTE GRAFT-VERSUS-HOST DISEASE. Medical Immunology (Russia). 2015;17(6):499-516. (In Russ.) https://doi.org/10.15789/1563-0625-2015-6-499-516

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