Cutting Edge: Tissue-Resident Memory T Cells Generated by Multiple Immunizations or Localized Deposition Provide Enhanced Immunity.
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 TRMare often concentrated at sites of prior infection, it has been shown that TRMcan disseminate throughout the body. We examined the relative effectiveness of global versus targeted CD8+TRMlodgment in skin. The site of initial T cell priming made little difference to skin lodgement, whereas local inflammation and Ag recognition enhanced TRMaccumulation and retention. Disseminated TRMlodgment 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 TRMnumbers and maximal protection against infection. Overall, these results highlight the potency of localized TRMdeposition as a means of pathogen control as well as demonstrating the limitations of global TRMlodgment.
Department of Microbiology and Immunology, Peter Doherty Institute for Infection and Immunity, The University of Melbourne, Melbourne, Victoria 3000, Australia.
Brooke
B
Davies
Department of Microbiology and Immunology, Peter Doherty Institute for Infection and Immunity, The University of Melbourne, Melbourne, Victoria 3000, Australia.
Julia E
JE
Prier
Department of Microbiology and Immunology, Peter Doherty Institute for Infection and Immunity, The University of Melbourne, Melbourne, Victoria 3000, Australia.
Claerwen M
CM
Jones
Department of Microbiology and Immunology, Peter Doherty Institute for Infection and Immunity, The University of Melbourne, Melbourne, Victoria 3000, Australia.
Thomas
T
Gebhardt
Department of Microbiology and Immunology, Peter Doherty Institute for Infection and Immunity, The University of Melbourne, Melbourne, Victoria 3000, Australia lkmackay@unimelb.edu.au fcarbone@unimelb.edu.au.
Francis R
FR
Carbone
Department of Microbiology and Immunology, Peter Doherty Institute for Infection and Immunity, The University of Melbourne, Melbourne, Victoria 3000, Australia lkmackay@unimelb.edu.au fcarbone@unimelb.edu.au.
Laura K
LK
Mackay
D000818:Animals; D017951:Antigen Presentation; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D002465:Cell Movement; D002478:Cells, Cultured; D064532:Histocompatibility Antigen H-2D / Q000235:genetics; D007117:Immunization, Secondary; D007156:Immunologic Memory; D007239:Infections / Q000276:immunology*; D007249:Inflammation / Q000276:immunology*; D008213:Lymphocyte Activation; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D012867:Skin / Q000276:immunology*
D064532:Histocompatibility Antigen H-2D