ТИМУС: СТРУКТУРА И ФУНКЦИЯ, НОРМА И ПАТОЛОГИЯ

Т-лимфоциты играют центральную роль в адаптивном иммунитете. Хелперные, цитотоксические,  регуляторные Т-клетки (Treg), нетрадиционные типы Т-клеток (γδT-клетки, естественные Т-клетки киллеры (NKT)), а также такие  подтипы Т-клеток, как инвариантные Т-клетки, ассоциированные со слизистой оболочкой MAIT) и интраэпителиальные лимфоциты CD8αα (lEL)) оказывают  помощь в  развитии гуморального иммунного ответа, уничтожении инфицированных и раковых клеток,  регуляции специфических и целевых иммунных реакций, достаточно успешно избегая при этом длительного воспаления и аутоиммунитета. Развитие Т- лимфоцитов осуществляется в несколько этапов, важнейшим из которых является формирование   аутотолерантности Т- клеток в тимусе. Являясь источником RTE (Recent Thymus Emigrant), наиболее ранних и антигенно наивных Т- клеток, выходящих из тимуса и фенотипически определяемых в периферической крови у человека, тимус создаёт необходимую среду для дифференцировки и селекции Т-клеток. Формирование центральной иммунной толерантности обусловлено взаимодействием наивных Т-клеток с микроокружением тимуса в медуллярной, корковой части и периваскулярном пространстве. Необходимое количество специфичных и аутотолерантных наивных клеток RTE, прошедших этапы отбора, постоянно экспортируется на периферию, способствуя установлению адаптивного иммунитета и центральной толерантности.

Сложные механизмы функционирования тимуса, обеспечивающие предотвращение аутоиммунных заболеваний с помощью процессов в корковом и мозговом веществе и включающие позитивный и негативный отбор и генерацию регуляторных Т-клеток (Tregs), воздействуют на структурный матрикс (кора и мозговое вещество) тимуса. Результаты этого воздействия зависят не только от среды, с которой контактирует организм, но и от изначальной структурной и функциональной устойчивости компонентов тимуса, недостаточность которых может привести к нарушениям и болезням органа, приводящем, в свою очередь, к сокрушительным последствиям для организма. Несмотря на сложности в изучении патогенеза аутоиммунных заболеваний, в настоящее время известно, что в их основе лежат нарушения структур, формирующих центральную аутотолерантность. Исследуется также вклад постепенного накопления генетических мутаций, изменения экспрессии генов, структурных и функциональных нарушений компонентов тимуса. Понимание молекулярных механизмов этих процессов необходимо для выявления диагностических биомаркеров, потенциальных контрольных точек и уточнения патогенеза аутоиммунных заболеваний, а также определяет возможные подходы к поддержанию или восстановлению функции тимуса и помогает разработать стратегии смягчения осложнений, связанных с инволюцией.

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