Nature immunology · 2025
CD4+ T cells license Kupffer cells to reverse CD8+ T cell dysfunction induced by hepatocellular priming.
СтатьяНазвание и аннотация: Перевод в очереди
Обработка статьи · этапы, ошибки и управление
Загрузка состояния…
Ошибки и ограничения
История · было → стало
Состояние обновляется каждые 5 секунд, пока блок открыт. Процент показывается только там, где известен объём работы. Пауза останавливает продолжение этапа; текущий запрос к источнику может завершиться.
Venzin Valentina, Beccaria Cristian G, Perucchini Chiara, Delfino Pietro, Bono Elisa B, Giustini Leonardo, Moalli Federica, Grillo Marta, Fumagalli Valeria, Laura Chiara, Di Lucia Pietro, Reinhard Katharina, Petschenka Jutta, Omokoko Tana Annmarie, Celant Anna, Ottolini Sabrina, Kawashima Keigo, Ravà Micol, De Giovanni Marco, Inverso Donato, Kuka Mirela, Kennedy Patrick T F, Guilliams Martin, Casorati Giulia, Pedica Federica, Ponzoni Maurilio, Şahin Uğur, Le Bert Nina, Bertoletti Antonio, Vascotto Fulvia, Guidotti Luca G, Iannacone Matteo
Аннотация
Chronic hepatitis B virus (HBV) infection is marked by dysfunctional HBV-specific CD8+ T cells, and restoring their effector activity is a major therapeutic goal. Here, we generated HBV-specific CD4+ T cell receptor transgenic mice to show that CD4+ effector T cells can prevent and reverse the CD8⁺ T cell dysfunction induced by hepatocellular priming. This rescue enhances antiviral CD8+ T cell function and suppresses viral replication. CD4+ T cell help occurs directly within the liver, independent of secondary lymphoid organs, and requires local antigen recognition. Kupffer cells, rather than dendritic cells, are the critical antigen-presenting platform. CD4+ T cells license Kupffer cells via CD40-CD40L interactions, triggering interleukin (IL)-12 and IL-27 production. IL-12 expands the CD4+ T cell pool, while IL-27 is essential for CD8+ T cell rescue. Exogenous IL-27 similarly restores HBV-specific CD8+ T cell function in mice and in T cells isolated from chronically infected patients. These findings identify IL-27 as a tractable immunotherapeutic target in chronic HBV infection.