Department of Hematopoiesis, Sanquin Research, Amsterdam, The Netherlands.
Department of Microbiology and Immunology, Peter Doherty Institute for Infection and Immunity, The University of Melbourne, Melbourne, Australia.
Eur J Immunol. 2019 Jun;49(6):853-872. doi: 10.1002/eji.201848003. Epub 2019 Apr 2.
BM has been put forward as a major reservoir for memory CD8 T cells. In order to fulfill that function, BM should "store" memory CD8 T cells, which in biological terms would require these "stored" memory cells to be in disequilibrium with the circulatory pool. This issue is a matter of ongoing debate. Here, we unequivocally demonstrate that murine and human BM harbors a population of tissue-resident memory CD8 T (T ) cells. These cells develop against various pathogens, independently of BM infection or local antigen recognition. BM CD8 T cells share a transcriptional program with resident lymphoid cells in other tissues; they are polyfunctional cytokine producers and dependent on IL-15, Blimp-1, and Hobit. CD8 T cells reside in the BM parenchyma, but are in close contact with the circulation. Moreover, this pool of resident T cells is not size-restricted and expands upon peripheral antigenic re-challenge. This works extends the role of the BM in the maintenance of CD8 T cell memory to include the preservation of an expandable reservoir of functional, non-recirculating memory CD8 T cells, which develop in response to a large variety of peripheral antigens.
BM 被认为是记忆性 CD8 T 细胞的主要储存库。为了发挥这一功能，BM 应该“储存”记忆性 CD8 T 细胞，从生物学角度来看，这就要求这些“储存”的记忆细胞与循环池处于不平衡状态。这个问题一直存在争议。在这里，我们明确地证明了鼠类和人类的 BM 中存在一群组织驻留记忆性 CD8 T（T）细胞。这些细胞是针对各种病原体发育的，与 BM 感染或局部抗原识别无关。BM CD8 T 细胞与其他组织中的固有淋巴细胞具有相似的转录程序；它们是多功能细胞因子的产生细胞，依赖于 IL-15、Blimp-1 和 Hobit。CD8 T 细胞位于 BM 实质中，但与循环系统密切接触。此外，这种驻留 T 细胞池不受大小限制，并在外周抗原再次刺激时扩增。这项工作扩展了 BM 在维持 CD8 T 细胞记忆中的作用，包括保存可扩增的功能性非循环记忆性 CD8 T 细胞储备，这些细胞是针对各种外周抗原发育的。
