Recent discoveries have expanded our understanding of how T cells are positioned within lymph nodes to enhance immune responses during infection. Upon activation by dendritic cells (DCs) in the paracortex of a draining lymph node, the chemokine receptor CXCR3 is rapidly upregulated on the surface of antigen-specific T cells. CXCR3 binds two ligands in C57BL/6 mice, CXCL9 and CXCL10, which are produced in the cortical ridge and interfollicular regions of draining lymph nodes and provide chemotactic signals to newly activated CXCR3+ T cells. While it is known that CXCR3+ T cell repositioning within these peripheral regions is required to mount optimal immune responses, the cellular partners that regulate CXCR3+ T cell location for this process are poorly understood.
Combining chemokine reporter mice with viral infection, we have characterised the cellular sources of CXCR3 ligands. We show that CXCL9 and CXCL10 chemokines are produced by distinct DC and stromal cell populations. Specifically, we show that CXCL9 is produced by type 1 conventional DCs (cDC1) whereas CXCL10 is produced by type 2 cDCs (cDC2), inflammatory monocytes and stromal cells. We have cleared and imaged intact lymph nodes using light sheet fluorescence microscopy (LSFM) to identify the location of chemokine expressing cells and quantify how unique chemokine expressing compartments influence T cell positioning following infection. We correlate T cells position with the formation of T cell effectors and stem-like memory precursors and dissect how this is influenced by specific CXCR3-mediated interactions. This work highlights the finely regulated choreography of T cell migration following viral infection and provides a platform to tune specific T cell differentiation outcomes.