Medical Research Seminar: Effector and stem-like memory cell fates are imprinted in distinct lymph node niches directed by CXCR3 ligands
Doctor Joanna Groom
Laboratory Head, Walter & Eliza Hall Institute of Medical Research
T cells dynamically interact with multiple, distinct cellular subsets to determine effector and memory differentiation. Here, we have developed a platform to quantify cell location in 3D, to determine the spatial requirements that direct T cell fate. Following LCMV infection, we demonstrated that CD8+ effector T cell differentiation is associated with positioning at the lymph node periphery. This was instructed by CXCR3 signaling, as in its absence, T cells remain confined to the lymph node center and alternatively differentiate into stem-like memory cell precursors. Using tissue clearing and light-sheet fluorescence microscopy we have provided a 3D map of the cellular sources of CXCR3 ligands. We demonstrate that CXCL9 and CXCL10 are expressed by spatially distinct dendritic and stromal cell subsets within lymph nodes. Finally, we demonstrate that T cell location can be tuned, through deficiency in CXCL10 or type I IFN signaling, to promote effector or stem-like memory fates.
Dr Groom’s research is focused on dissecting the T cell interactions that control immune function and maintenance of memory. This interest was piqued during her PhD, at the Garvan Institute, investigating the cellular signalling critical to lupus autoimmunity. Her research revealed a novel mechanism of autoantibody production, which was pivotal in licensing the BAFF blocking antibody, Belimumab for lupus treatment. During her postdoctoral fellowship at Harvard/Massachusetts General Hospital, Dr Groom discovered a new role for inflammatory chemokines in T cell priming. Dr Groom is a Laboratory Head in the Immunology Division at the Walter and Eliza Hall Institute and WEHI CSL Centenary fellow. Dr Groom combines in vivo and 3D imaging methods with transcriptional analysis to discover how cellular interactions lead to tailored protection against diverse pathogenic infections. Dr Groom’s current work investigates the pathogen-specific tailoring of T follicular helper responses and how the CXCR3 chemokine system balances T cell fate between effector function and to establish long-term protective memory.
Read more about Dr Joanna Groom’s work here.
Download the poster here.