Effector and stem-like memory cell fates are imprinted in distinct lymph node niches directed by CXCR3 ligands
Publication Year 2021-04,Volume 22,Issue #4,Page 434-448
Journal Title
Nature Immunology
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.
Animals; Arenaviridae Infections/genetics/immunology/*metabolism/virology; CD8-Positive T-Lymphocytes/immunology/*metabolism/virology; *Cell Differentiation; Cell Lineage; Cells, Cultured; Chemokine CXCL10/genetics/*metabolism; Chemokine CXCL9/genetics/*metabolism; Chemotaxis, Leukocyte; Dendritic Cells/immunology/metabolism; Disease Models, Animal; Host-Pathogen Interactions; *Immunologic Memory; Interferon Type I/metabolism; Ligands; Lymph Nodes/immunology/*metabolism/virology; Lymphocytic choriomeningitis virus/immunology/pathogenicity; Mice, Inbred C57BL; Mice, Knockout; Phenotype; Precursor Cells, T-Lymphoid/immunology/*metabolism/virology; Receptor, Interferon alpha-beta/genetics/metabolism; Receptors, CCR7/metabolism; Receptors, CXCR3/genetics/*metabolism; Signal Transduction; Stem Cell Niche; Stromal Cells/immunology/metabolism
WEHI Research Division(s)
Immunology; Advanced Technology And Biology
PubMed ID
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Creation Date: 2021-06-30 12:00:52
Last Modified: 2021-07-20 02:47:00
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