广泛用于预防结核病的疫苗卡介苗（BCG）对成年人保护效果差，如何增强BCG诱导的记忆性免疫应答是结核病防治的关键科学问题。效应记忆性和组织定居记忆性T细胞（TEM/TRM）能迅速在组织局部对抗原产生免疫应答，是再次应答中直接发挥作用的主体细胞。我们前期研究发现结核菌（M.tb）/BCG脂糖抗原能刺激宿主细胞分泌IL-10，IL-10下调CD4+T细胞重要功能分子CD44表达，故推测IL-10下调CD44后可能抑制了BCG诱导的记忆性细胞形成。本项目拟阐明BCG免疫过程中IL-10下调CD44表达、CD44介导细胞骨架重构和迁移以及相关肺内记忆性CD4+TEM/TRM细胞形成机制，并通过在小鼠模型中拮抗IL-10作用来提高BCG的免疫效能。项目的开展将帮助阐明IL-10和CD44在记忆性CD4+TEM/TRM细胞形成中发挥的作用机制，为寻找提高BCG免疫记忆效能的新靶点奠定基础。

Bacillus Calmette–Guérin (BCG) vaccine, which is widely used to prevent tuberculosis, has a limited duration of protection and has shown controversial and variable levels of efficacy, especially against pulmonary TB in adults. How to improve the memory immune response induced by BCG is a key scientific issue in tuberculosis prevention and treatment. The memory cells CD4+TEM/TRM (effector memory T cells and tissue resident T cells) rapidly produce immune response to antigens. We previously reported that M.tb/BCG lipoglycan antigen induced host cells to produce IL-10. We found that CD44, the multifunctional cell surface adhesion molecule on CD4+ T cells, was downregulated in the presence of IL-10. These results suggest that IL-10 might inhibit CD44 expression and hinder the development of BCG-induced immune memory. In our current work, we plan to investigate the mechanisms of IL-10-regulated CD44 expression, CD44-mediated cytoskeletal rearrangement and cell migration, as well as the development of CD4+TEM/TRM in the lung during BCG immunization. Then we will block the IL-10 effect in vivo and assess the development of CD4+TEM/TRM in the lung during BCG immunization. Our work will provide new information of IL-10-regulated and CD44-medicated CD4+TEM/TRM formation in the lung, and contribute to developing the new strategy for improving the efficacy of the BCG-induced immune memory.