Division of Immunology, Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria, Australia.
Department of Medical Biology, University of Melbourne, Parkville, Victoria, Australia.
Nat Immunol. 2021 Apr;22(4):434-448. doi: 10.1038/s41590-021-00878-5. Epub 2021 Mar 1.
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 细胞与多个不同的细胞亚群动态相互作用，以决定效应器和记忆细胞的分化。在这里，我们开发了一个平台来定量三维空间中的细胞位置，以确定直接影响 T 细胞命运的空间要求。在病毒感染后，我们证明 CD8 效应 T 细胞的分化与淋巴结外周的定位有关。这是由 CXCR3 信号指导的，因为在缺乏 CXCR3 信号的情况下，T 细胞被局限在淋巴结中心，并可替代地分化为类干细胞记忆细胞前体。通过绘制 CXCR3 配体的细胞来源图，我们证明了 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，类干细胞记忆前体在皮质旁区的保留与 CCR7 的表达有关。最后，我们证明通过缺乏 CXCL10 或 I 型干扰素信号，可以调整 T 细胞的位置，以促进效应器或类干细胞记忆的命运。
