Route of priming regulates access to residual antigen and migration of memory T cells (49.12)

Abstract

Abstract Memory T cells resident in peripheral tissues are key to establishing protective immunity to pathgens. There exist seemingly paradoxical concepts in the understanding of mechanisms regulating tissue-specific migration of CD8 memory T cells. One concept is that tissue-specific homing is imprinted by exposure to environmental factors during T cell priming. A contrasting concept is that memory T cells acquire tissue-specific homing properties through continued maturation in the periphery. Our mouse models of respiratory virus infection demonstrate that continued recruitment of CD8 T cells to the airways during steady-state memory is mediated by sequential events. Initial priming of CD8 T cells in the lung draining lymph node imprints memory CD8 T cells with the capacity to access residual antigen depots. Stimulation by residual antigen in the weeks to months following resolution of infection then promotes continued maturation and airway migration of CD8 T cells during steady-state memory. Interestingly, despite the formation of residual antigen depots following intraperitoneal, subcutaneous, or intramuscular infection, the resulting memory T cells ignore this maturation stimulus and fail to migrate to the airways despite exposure to lung inflammation. We hypothesize the site of priming is critical for imprinting memory T cells with the ability to access the additional signals required for continued maturation and effective migration of memory T cells to peripheral tissues.