Cutting Edge: Tissue-Resident Memory T Cells Generated by Multiple Immunizations or Localized Deposition Provide Enhanced Immunity

Abstract Tissue-resident memory T cells (TRM) have been shown to afford superior protection against infection, particularly against pathogens that enter via the epithelial surfaces of the body. Although TRM are often concentrated at sites of prior infection, it has been shown that TRM can disseminate throughout the body. We examined the relative effectiveness of global versus targeted CD8+ TRM lodgment in skin. The site of initial T cell priming made little difference to skin lodgement, whereas local inflammation and Ag recognition enhanced TRM accumulation and retention. Disseminated TRM lodgment was seen with the skin, but required multiple exposures to Ag and was inferior to targeted strategies. As a consequence, active recruitment by inflammation or infection resulted in superior TRM numbers and maximal protection against infection. Overall, these results highlight the potency of localized TRM deposition as a means of pathogen control as well as demonstrating the limitations of global TRM lodgment.