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

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