Effector and stem-like memory cell fates are imprinted in distinct lymph node niches directed by CXCR3 ligands
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
Nature Immunology | NATURE RESEARCH | Published : 2021
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 distin..View full abstract
Awarded by National Health and Medical Research Council (NHMRC)
Awarded by Australian Research Council Future Fellowship
Awarded by NHMRC
We thank S. L. Nutt, K. L. Good-Jacobson and K. D. Shortman for helpful discussions and/or critical reading of the manuscript. This work was supported by National Health and Medical Research Council (NHMRC) Ideas (no. GNT1182649) and Project (no. GNT1137989) grants to J.R.G.; grant nos. GNT1006592, GNT1045549 and GNT1065626 to M.P.; and grant no. GNT1185513 to L.A.M. B.C.D. is supported by a WEHI Academic Excellence scholarship. A.A.S. and L.D. are supported by Melbourne research scholarships. J.R.G. was supported by an Australian Research Council Future Fellowship (no. FT130100708) and is supported by a Walter and Eliza Hall Centenary Fellowship sponsored by CSL Behring. M.P. is supported by an NHMRC Investigator (no. GNT1175011) and Sylvia & Charles Viertel Senior Medical Research Fellowships. L.A.M. is supported by a Victorian Cancer Agency mid-career fellowship. The experimental scheme figures were generated with BioRender. This work was made possible through the Victorian State Government Operational Infrastructure Support and Australian Government NHMRC Independent Research Institutes Infrastructure Support Scheme.