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

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