Department of Immunology, Institute of Medical Microbiology and Hygiene, University of Freiburg, Freiburg, Germany.
Eur J Immunol. 2013 Sep;43(9):2295-304. doi: 10.1002/eji.201343519. Epub 2013 Jun 26.
The thymus is a primary lymphoid organ responsible for production and selection of T cells. Nonetheless, mature T cells and in particular activated T cells can reenter the thymus. Here, we identified memory CD8(+) T cells specific for lymphocytic choriomeningitis virus or vaccinia virus in the thymus of mice long-time after the infection. CD8(+) T cells were mainly located in the thymic medulla, but also in the cortical areas. Interestingly, virus-specific memory CD8(+) T cells in the thymus expressed the cell surface markers CD69 and CD103 that are characteristic of tissue-resident memory T cells in a time-dependent manner. Kinetic analyses and selective depletion of peripheral CD8(+) T cells by antibodies further revealed that thymic virus-specific memory CD8(+) T cells did not belong to the circulating pool of lymphocytes. Finally, we demonstrate that these thymus-resident virus-specific memory CD8(+) T cells efficiently mounted a secondary proliferative response, exhibited immediate effector functions and were able to protect the thymus from lymphocytic choriomeningitis virus reinfection. In conclusion, the present study not only describes for the first time virus-specific memory CD8(+) T cells with characteristics of tissue-resident memory T (T(RM)) cells in a primary lymphoid organ but also extends our knowledge about local T-cell immunity in the thymus.
胸腺是负责 T 细胞产生和选择的主要淋巴器官。尽管如此，成熟的 T 细胞，特别是激活的 T 细胞，可以重新进入胸腺。在这里，我们在感染后很长时间的小鼠胸腺中鉴定出针对淋巴细胞性脉络丛脑膜炎病毒或牛痘病毒的记忆性 CD8(+)T 细胞。CD8(+)T 细胞主要位于胸腺髓质，但也存在于皮质区。有趣的是，胸腺中的病毒特异性记忆性 CD8(+)T 细胞以时间依赖性方式表达组织驻留记忆 T 细胞的表面标记物 CD69 和 CD103。动力学分析和通过抗体选择性耗尽外周血 CD8(+)T 细胞进一步表明，胸腺内的病毒特异性记忆性 CD8(+)T 细胞不属于循环淋巴细胞池。最后，我们证明这些胸腺内驻留的病毒特异性记忆性 CD8(+)T 细胞能够有效地进行二次增殖反应，表现出即刻的效应功能，并能够保护胸腺免受淋巴细胞性脉络丛脑膜炎病毒的再感染。总之，本研究不仅首次描述了主要淋巴器官中具有组织驻留记忆 T（T(RM)）细胞特征的病毒特异性记忆性 CD8(+)T 细胞，而且还扩展了我们对胸腺内局部 T 细胞免疫的认识。
