LN CD8+ resident memory T cells demonstrate unexpected abundance, exhibit biased migration upon recall, and orchestrate intranodal recall responses 4178

Abstract

Abstract Description For over six decades, LNs have been considered sites of lymphocyte recirculation, with central memory T cells (TCM) assuming the role of primary surveillants. We and others have identified CD8+ memory T cells that establish residency within the LNs (LN TRM), expanding our view of LN immunosurveillance. However, the contribution of LN TRM to host immunity is largely unknown. Here we utilized numerous murine infection models, quantitative immunofluorescent microscopy, and parabiosis surgery to investigate LN TRM abundance, longevity, and function. We demonstrated that mechanical dissociation underestimates the density of LN TRM, and enzymatic digestion revealed that LN TRM account for over 50% of memory T cells in some LNs. Parabiosis surgery revealed that TRM occupy distinct niches in LNs including B cell follicles and the subcapsular sinus. Functionally, compared to TCM, LN TRM more robustly react to recurrent antigen via proinflammatory cytokine production. Further, LN TRM orchestrate intranodal recall responses by bolstering TCM activation, innate cell recruitment, and myeloid cell activation. Despite residency at homeostasis, LN TRM constitutively express tissue-specific homing molecules perhaps positioning them for rapid deployment. Following adoptive transfer and recall, compared to TCM, LN TRM preferentially home to upstream tissues. Thus, in the event of pathogen reemergence, LN TRM make specialized contributions to LN immunosurveillance and regional recall responses. Funding Sources Supported by NIH/NIAID F31 AI176750 Topic Categories Mucosal and Regional Immunology (MUC)