Using 3D imaging, Duckworth, Lafouresse, and Wimmer et al. showed that following LCMV infection, transferred LCMV-specific CD8+ T cells expressing a T-bet reporter migrated from the central paracortex to the peripheral interfollicular regions of lymph nodes and differentiated into short-lived Teff cells. CXCR3 ligands CXCL9 or CXCL10, expressed by different DC and stromal cell subsets, induced spatially distinct migration within lymph nodes. The CCR7/CCL21 axis retained transferred Cxcr3-/- cells in the paracortex with a polyfunctional TCF1+ TSCM fate. Deficits in IFN-I signals, which induce CXCR3 ligands, led to paracortical localization and TSCM cell fate.
Contributed by Paula Hochman
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.