Freud Aharon G, Becknell Brian, Roychowdhury Sameek, Mao Hsiaoyin C, Ferketich Amy K, Nuovo Gerard J, Hughes Tiffany L, Marburger Trent B, Sung John, Baiocchi Robert A, Guimond Martin, Caligiuri Michael A
Department of Molecular Virology, Immunology, and Medical Genetics, College of Medicine and Public Health, The Ohio State University, Columbus, Ohio 43210, USA.
Immunity. 2005 Mar;22(3):295-304. doi: 10.1016/j.immuni.2005.01.013.
In humans, T cells differentiate in thymus and B cells develop in bone marrow (BM), but the natural killer (NK) precursor cell(s) and site(s) of NK development are unclear. The CD56bright NK subset predominates in lymph nodes (LN) and produces abundant cytokines compared to the cytolytic CD56dim NK cell that predominates in blood. Here, we identify a novel CD34dimCD45RA(+) hematopoietic precursor cell (HPC) that is integrin alpha4beta7bright. CD34dimCD45RA(+)beta7bright HPCs constitute <1% of BM CD34(+) HPCs and approximately 6% of blood CD34(+) HPCs, but >95% of LN CD34(+) HPCs. They reside in the parafollicular T cell regions of LN with CD56bright NK cells, and when stimulated by IL-15, IL-2, or activated LN T cells, they become CD56bright NK cells. The data identify a new NK precursor and support a model of human NK development in which BM-derived CD34dimCD45RA(+)beta7bright HPCs reside in LN where endogenous cytokines drive their differentiation to CD56bright NK cells in vivo.
在人类中，T细胞在胸腺中分化，B细胞在骨髓（BM）中发育，但自然杀伤（NK）前体细胞和NK发育位点尚不清楚。与在血液中占主导地位的细胞毒性CD56dim NK细胞相比，CD56bright NK亚群在淋巴结（LN）中占主导地位，并产生大量细胞因子。在这里，我们鉴定出一种新的整合素α4β7bright的CD34dimCD45RA(+)造血前体细胞（HPC）。CD34dimCD45RA(+)β7bright HPCs在BM CD34(+) HPCs中占比不到1%，在血液CD34(+) HPCs中约占6%，但在LN CD34(+) HPCs中占比超过95%。它们与CD56bright NK细胞一起存在于LN的滤泡旁T细胞区域，当受到IL-15、IL-2或活化的LN T细胞刺激时，它们会变成CD56bright NK细胞。这些数据鉴定出一种新的NK前体，并支持一种人类NK发育模型，即BM来源的CD34dimCD45RA(+)β7bright HPCs存在于LN中，内源性细胞因子在体内驱动它们分化为CD56bright NK细胞。
