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Title: Effector and stem-like memory cell fates are imprinted in distinct lymph node niches directed by CXCR3 ligands.
Austin Authors: Duckworth, Brigette C;Lafouresse, Fanny;Wimmer, Verena C;Broomfield, Benjamin J;Dalit, Lennard;Alexandre, Yannick O;Sheikh, Amania A;Qin, Raymond Z;Alvarado, Carolina;Mielke, Lisa A;Pellegrini, Marc;Mueller, Scott N;Boudier, Thomas;Rogers, Kelly L;Groom, Joanna R
Affiliation: Centre de Recherches en Cancérologie de Toulouse, INSERM U1037, Equipe Labellisée Ligue Nationale Contre le Cancer, Université de Toulouse III-Paul Sabatier, Toulouse, France
The Australian Research Council Centre of Excellence in Advanced Molecular Imaging, The University of Melbourne, Melbourne, Victoria, Australia
Department of Microbiology and Immunology, The University of Melbourne, at the Peter Doherty Institute for Infection and Immunity, Melbourne, Victoria, Australia
Division of Infection and Immunity, Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria, Australia
Division of Immunology, Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria, Australia
Sorbonne Université, Paris, France
Centre for Dynamic Imaging, Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria, Australia
Department of Medical Biology, University of Melbourne, Parkville, Victoria, Australia
Olivia Newton-John Cancer Research Institute
La Trobe University School of Cancer Medicine, Heidelberg, Victoria, Australia
Issue Date: Apr-2021 2021-03-01
Publication information: Nature Immunology 2021; 22(4): 434-448
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.
DOI: 10.1038/s41590-021-00878-5
ORCID: 0000-0002-2134-3542
Journal: Nature Immunology
PubMed URL: 33649580
Type: Journal Article
Appears in Collections:Journal articles

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