澳大利亚墨尔本大学Joanna R. Groom、Brigette C. Duckworth等研究人员合作发现，效应子和干细胞样记忆细胞的命运受不同淋巴结微环境所调节。2021年3月1日，《自然—免疫学》杂志在线发表了这项成果。

研究人员开发了一个平台，可以在三个维度上量化细胞位置，从而确定指导T细胞命运的空间要求。在病毒感染后，研究人员证明CD8⁺效应T细胞分化与在淋巴结外围的定位有关。这是由CXCR3信号指示的，因为在没有T细胞的情况下，T细胞被限制在淋巴结中心，并且可以分化为干样记忆细胞前体。

通过映射CXCR3配体的细胞来源，研究人员证明了CXCL9和CXCL10由空间上不同的树突状细胞和基质细胞亚群表达。与效应细胞不同，干细胞样记忆前体在皮层旁的保留与CCR7表达有关。

最后，研究人员证明可以通过CXCL10缺失或I型干扰素信号传导来调节T细胞的位置，从而促进效应子或干细胞样的记忆命运。

据了解，T细胞与多个不同的细胞亚群动态相互作用，从而确定效应子和记忆的分化。 

附：英文原文

Title: Effector and stem-like memory cell fates are imprinted in distinct lymph node niches directed by CXCR3 ligands

Author: Brigette C. Duckworth, Fanny Lafouresse, Verena C. Wimmer, Benjamin J. Broomfield, Lennard Dalit, Yannick O. Alexandre, Amania A. Sheikh, Raymond Z. Qin, Carolina Alvarado, Lisa A. Mielke, Marc Pellegrini, Scott N. Mueller, Thomas Boudier, Kelly L. Rogers, Joanna R. Groom

Issue&Volume: 2021-03-01

Abstract: T cells dynamically interact with multiple, distinct cellular subsets to determine effector and memory differentiation. Here, we developed a platform to quantify cell location in three dimensions to determine the spatial requirements that direct T cell fate. After viral infection, we demonstrated that CD8+ effector T cell differentiation is associated with positioning at the lymph node periphery. This was instructed by CXCR3 signaling since, in its absence, T cells are confined to the lymph node center and alternatively differentiate into stem-like memory cell precursors. By mapping the cellular sources of CXCR3 ligands, we demonstrated that CXCL9 and CXCL10 are expressed by spatially distinct dendritic and stromal cell subsets. Unlike effector cells, retention of stem-like memory precursors in the paracortex is associated with CCR7 expression. Finally, we demonstrated that T cell location can be tuned, through deficiency in CXCL10 or type I interferon signaling, to promote effector or stem-like memory fates. T cells are highly dynamic and their spatial and cellular interactions can influence their differentiation program. Groom and colleagues use three-dimensional spatial imaging to show that effector and stem-like memory cell fates are imposed within distinct lymph node regions.

DOI: 10.1038/s41590-021-00878-5

Source: https://www.nature.com/articles/s41590-021-00878-5