title: IL-15-Independent Maintenance of Tissue-Resident and Boosted Effector Memory CD8 T Cells.
abstract: IL-15 regulates central and effector memory CD8 T cell (TCM and TEM, respectively) homeostatic proliferation, maintenance, and longevity. Consequently, IL-15 availability hypothetically defines the carrying capacity for total memory CD8 T cells within the host. In conflict with this hypothesis, previous observations demonstrated that boosting generates preternaturally abundant TEM that increases the total quantity of memory CD8 T cells in mice. In this article, we provide a potential mechanistic explanation by reporting that boosted circulating TEM do not require IL-15 for maintenance. We also investigated tissue-resident memory CD8 T cells (TRM), which protect nonlymphoid tissues from reinfection. We observed up to a 50-fold increase in the total magnitude of TRM in mouse mucosal tissues after boosting, suggesting that the memory T cell capacity in tissues is flexible and that TRM may not be under the same homeostatic regulation as primary central memory CD8 T cells and TEM Further analysis identified distinct TRM populations that depended on IL-15 for homeostatic proliferation and survival, depended on IL-15 for homeostatic proliferation but not for survival, or did not depend on IL-15 for either process. These observations on the numerical regulation of T cell memory indicate that there may be significant heterogeneity among distinct TRM populations and also argue against the common perception that developing vaccines that confer protection by establishing abundant TEM and TRM will necessarily erode immunity to previously encountered pathogens as the result of competition for IL-15.
authors.affiliation: Department of Microbiology and Immunology, University of Minnesota, Minneapolis, MN 55455; Center for Immunology, University of Minnesota, Minneapolis, MN 55455;
authors.forename: Jason M
authors.initials: JM
authors.lastname: Schenkel
authors.affiliation: Department of Microbiology and Immunology, University of Minnesota, Minneapolis, MN 55455; Center for Immunology, University of Minnesota, Minneapolis, MN 55455;
authors.forename: Kathryn A
authors.initials: KA
authors.lastname: Fraser
authors.affiliation: Department of Microbiology and Immunology, University of Minnesota, Minneapolis, MN 55455; Center for Immunology, University of Minnesota, Minneapolis, MN 55455;
authors.forename: Kerry A
authors.identifier: 0000-0001-7194-8585
authors.initials: KA
authors.lastname: Casey
authors.affiliation: Department of Microbiology and Immunology, University of Minnesota, Minneapolis, MN 55455; Center for Immunology, University of Minnesota, Minneapolis, MN 55455;
authors.forename: Lalit K
authors.identifier: 0000-0002-8597-3949
authors.initials: LK
authors.lastname: Beura
authors.affiliation: Department of Microbiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104; and Institute for Immunology, Perelman School of Medicine; University of Pennsylvania, Philadelphia, PA 19104.
authors.forename: Kristen E
authors.initials: KE
authors.lastname: Pauken
authors.affiliation: Department of Microbiology and Immunology, University of Minnesota, Minneapolis, MN 55455; Center for Immunology, University of Minnesota, Minneapolis, MN 55455;
authors.forename: Vaiva
authors.initials: V
authors.lastname: Vezys
authors.affiliation: Department of Microbiology and Immunology, University of Minnesota, Minneapolis, MN 55455; Center for Immunology, University of Minnesota, Minneapolis, MN 55455; masopust@umn.edu.
authors.forename: David
authors.initials: D
authors.lastname: Masopust
mesh_terms: D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D049109:Cell Proliferation; D002478:Cells, Cultured; D003602:Cytotoxicity, Immunologic; D006706:Homeostasis; D007117:Immunization, Secondary; D007156:Immunologic Memory; D019409:Interleukin-15 / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D009092:Mucous Membrane / Q000276:immunology*; D016176:T-Lymphocyte Subsets / Q000276:immunology*; D014765:Viral Vaccines / Q000276:immunology
chemical_list: D019409:Interleukin-15; D014765:Viral Vaccines