title: Cutting edge: generation of effector cells that localize to mucosal tissues and form resident memory CD8 T cells is controlled by mTOR.
abstract: Mucosal tissues are subject to frequent pathogen exposure and are major sites for transmission of infectious disease. CD8 T cells play a critical role in controlling mucosa-acquired infections even though their migration into mucosal tissues is tightly regulated. The mechanisms and signals that control the formation of tissue-resident memory CD8 T cells are poorly understood; however, one key regulator of memory CD8 T cell differentiation, mammalian target of rapamycin kinase, can be inhibited by rapamycin. We report that, despite enhancing the formation of memory CD8 T cells in secondary lymphoid tissues, rapamycin inhibits the formation of resident memory CD8 T cells in the intestinal and vaginal mucosa. The ability of rapamycin to block the formation of functional resident CD8 T cells in mucosal tissues protected mice from a model of CD8 T cell-mediated lethal intestinal autoimmunity. These findings demonstrate an opposing role for mammalian target of rapamycin in the formation of resident versus nonresident CD8 T cell immunity.
authors: Department of Immunology and Microbiology, Rush University Medical Center, Chicago, IL 60612;
authors: Ryan T
authors: RT
authors: Sowell
authors: Department of Immunology and Microbiology, Rush University Medical Center, Chicago, IL 60612;
authors: Magdalena
authors: M
authors: Rogozinska
authors: Department of Microbiology, University of Minnesota, Minneapolis, MN 55455; and Center for Immunology, University of Minnesota, Minneapolis, MN 55455.
authors: Christine E
authors: CE
authors: Nelson
authors: Department of Microbiology, University of Minnesota, Minneapolis, MN 55455; and Center for Immunology, University of Minnesota, Minneapolis, MN 55455.
authors: Vaiva
authors: V
authors: Vezys
authors: Department of Immunology and Microbiology, Rush University Medical Center, Chicago, IL 60612; Amanda_Marzo@rush.edu.
authors: Amanda L
authors: AL
authors: Marzo
mesh_terms: D000818:Animals; D015551:Autoimmunity / Q000502:physiology; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology*; D005260:Female; D018928:Immunity, Mucosal / Q000502:physiology*; D007156:Immunologic Memory / Q000502:physiology*; D007413:Intestinal Mucosa / Q000166:cytology / Q000293:injuries*; D051379:Mice; D018448:Models, Immunological; D058570:TOR Serine-Threonine Kinases / Q000276:immunology*; D014621:Vagina / Q000166:cytology / Q000276:immunology
chemical_list: C546843:mTOR protein, mouse; D058570:TOR Serine-Threonine Kinases