mimmunМедицинская иммунологияMedical Immunology (Russia)1563-06252313-741XSPb RAACI10.15789/1563-0625-MOI-1768mimmun-1768Research ArticleОБЗОРЫREVIEWSМеханизмы иммунорегуляции и трансплантационный иммунитет при пересадках роговицыMechanisms of immune regulation and transplantation immunity in corneal transplantsНероевВ. В.NeroevV. V.

Нероев В.В. – д.м.н., профессор, член-корр. РАН, директор

105062, Москва, ул. Садовая-Черногрязская, 14/19

Neroev V.V., PhD, MD (Medicine), Professor, Corresponding Member, Russian Academy of Sciences, Director

105062, Moscow, Sadovaya-Chernogryazskaya str., 14/19.

info@igb.ruБалацкаяН. В.BalatskayaN. V.

Балацкая Н.В. – к.б.н., ведущий научный сотрудник, руководитель отдела иммунологии и вирусологии

105062, Москва, ул. Садовая-Черногрязская, 14/19

Balatskaya N.V., PhD (Biology), Leading Research Associate, Head, Department of Immunology and Virology

105062, Moscow, Sadovaya-Chernogryazskaya str., 14/19.

balnat07@rambler.ruЧенцоваЕ. В.ChentsovaE. V.

Ченцова Е.В. – д.м.н., профессор, руководитель отдела травматологии и реконструктивной хирургии

105062, Москва, ул. Садовая-Черногрязская, 14/19

Chentsova E.V., PhD, MD (Medicine), Professor, Head, Department of Traumatology and Reconstructive Surgery

105062, Moscow, Sadovaya-Chernogryazskaya str., 14/19.

chentsova27@yandex.ruШамхаловаХ. М.ShamkhalovaKh. M.

Шамхалова Х.М. – аспирант отдела иммунологии и вирусологии

105062, Москва, ул. Садовая-Черногрязская, 14/19

Shamkhalova Kh.M., Postgraduate Student, Department of Immunology and Virology

105062, Moscow, Sadovaya-Chernogryazskaya str., 14/19.

dr.murnika@gmail.comФГБУ «Национальный медицинский исследовательский центр глазных болезней имени Гельмгольца» Министерства здравоохранения РФРоссияHelmholtz National Medical Research Center of Eye DiseasesRussian Federation2020290120202216176Copyright © Нероев В.В., Балацкая Н.В., Ченцова Е.В., Шамхалова Х.М., 20202020Нероев В.В., Балацкая Н.В., Ченцова Е.В., Шамхалова Х.М.Neroev V.V., Balatskaya N.V., Chentsova E.V., Shamkhalova K.M.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/1768

На сегодняшний день трансплантация роговицы (кератопластика) относится к наиболее частым операциям по пересадкам солидных тканей в мире, и, в отличие от последних, эта форма вмешательства нередко выполняется без применения тканевого типирования и системной иммуносупрессии.

Высокая частота прозрачного приживления роговичного трансплантата (до 90% случаев), при условии отсутствия факторов риска, обусловлена особыми механизмами иммунной привилегии в переднем отрезке глаза (функционально-структурном объединении роговицы и передней камеры (ПК)), реализуемой посредством локальной и системной иммунорегуляции: феномена иммунного отклонения, связанного с ПК глаза (ACAID), компонентов внутренней жидкой среды – водянистой влаги ПК, обладающих иммуносупрессорными свойствами – IL-1ra, TSP-1, TGF-β2, регуляторных белков системы комплемента, α-MSH (альфа-меланоцит стимулирующего гормона), VIP (вазоактивного интестинального пептида), индоламин 2,3-диоксигеназы (IDO), кальцитонин-ген-связанного пептида (CGRP), соматостатина и др.

Помимо ACAID и компонентов ВПК, вклад в поддержание иммунной привилегии (имеющей чрезвычайно важное значение для успешного исхода кератопластики) вносят и другие механизмы, поддерживаемые, в частности, иммунологически активными мембраноассоциированными молекулами клеток эндотелия роговицы PDL-1 (лигандом программируемой клеточной гибели 1), а также sVEGFR-1, sVEGFR-2, sVEGFR-3, участвующими в поддержании аваскулярности роговичной ткани. Нарушение иммунной привилегии роговицы создает условия для активации распознавания, включения эффекторных механизмов трансплантационного иммунитета и в дальнейшем с большой вероятностью может привести к развитию реакции тканевой несовместимости и помутнению кератотрансплантата.

Отторжение трансплантата может быть локализовано в любом из клеточных слоев роговицы, включая эпителий, строму и эндотелий. Отторжение эндотелия относится к наиболее тяжелой для зрительных функций форме, что обусловлено невозможностью восстановления эндотелиальных клеток роговицы, накоплением в ней воды вследствие нарушения функций эндотелиоцитов. Отторжение трансплантата клинически характеризуется его отеком и наличием воспалительных клеток, как циркулирующих в передней камере, так и в виде преципитатов на эндотелиальных клетках трансплантата.

С повышенным риском отторжения трансплантата роговицы ассоциирован ряд факторов, включая: степень воспаления и/или васкуляризации трансплантационного ложа (места размещения донорской роговицы), повторная кератопластика, аллосенсибилизация (вследствие других пересадок солидных органов, в том числе костного мозга, переливания крови, беременности и т. д.), аллергические и системные заболевания.

В настоящем обзоре проанализированы и систематизированы данные литературы, посвященной исследованиям факторов иммунной привилегии роговицы и феномена ACAID, их роли в формировании аллотолерантности при трансплантации роговицы, выделены основные условия, необходимые для запуска реакции тканевой несовместимости, обсуждаются механизмы аллогенного распознавания и эффекторной стадии иммунного ответа, деструкции роговичного аллотрансплантата.

At the present time, corneal transplantation (keratoplasty) is one of the most frequent modes of solid tissue transplants in the world. Unlike other kinds of transplants, corneal grafting is often performed without tissue typing and systemic immunosuppression.

High frequency of transparent corneal engraftment (up to 90% of cases) in the absence of risk factors is due to special immunoprivileged area in the anterior eye segment (functionally, a structural aggregation of the cornea and anterior chamber, AC) accomplished by local and systemic immunoregulatory mechanisms, i.e., phenomenon of immune deviation associated with anterior chamber of the eye (ACAID), components of the internal liquid medium, a watery moisture with immunosuppressive properties, e.g., IL-1ra, TSP-1,TGF-β2, regulatory complement proteins, α-MSH (alpha-melanocyte stimulating hormone), VIP (vasoactive intestinal peptide), indolamine 2,3-dioxygenase (IDO), calcitonin-gene-bound peptide (CGRP), somatostatin, etc.

In addition to ACAID and liquid AC components, a contribution to the maintenance of immune privilege which is extremely important for a successful outcome of keratoplasty, is provided by other mechanisms, in particular, immunologically active membrane-associated molecules of corneal endothelium, i.e., PDL-1 (Programmed death ligand 1), and sVEGFR-1, sVEGFR-2, sVEGFR-3 involved in maintaining avascularity of the corneal tissue. Disturbances of the immune privilege of the cornea promotes activation of immune recognition with switching the effector mechanisms of transplantation immunity, thus leading to subsequent development of the tissue incompatibility reaction and clouding of transplanted cornea. Graft rejection can be localized in any of the corneal cell layers, including epithelium, stroma, and endothelium. Endothelial rejection causes the most severe affection of visual functions, due to the inability of local endothelial recovery, and water accumulation due to the endothelial dysfunction.

Graft rejection is clinically characterized by edema and the presence of inflammatory cells, either circulating in the anterior chamber, or forming precipitates on the graft endothelial cells.

A number of factors are associated with an increased risk of corneal graft rejection, including the degree of inflammation and/or vascularization of the transplant bed i.e., location of the donor cornea, repeated keratoplasty, allosensitization due to other cellular transplants, including bone marrow, blood transfusions, pregnancy, etc., as well as allergic and systemic diseases.

This review article considers and systematizes the data from the literature concerning studies of the factors determining the immune privileged state of cornea, and the ACAID phenomenon, their role in development of allotolerance in corneal transplantation, highlights the main conditions required for triggering the tissue incompatibility reactions, discusses the mechanisms of allogeneic recognition and effector stage of the immune response, destruction of corneal allografts.

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