title: Sensing and alarm function of resident memory CD8⁺ T cells.
abstract: CD8(+) T cells eliminate intracellular infections through two contact-dependent effector functions: cytolysis and secretion of antiviral cytokines. Here we identify the following additional function for memory CD8(+) T cells that persist at front-line sites of microbial exposure: to serve as local sensors of previously encountered antigens that precipitate innate-like alarm signals and draw circulating memory CD8(+) T cells into the tissue. When memory CD8(+) T cells residing in the female mouse reproductive tract encountered cognate antigen, they expressed interferon-γ (IFN-γ), potentiated robust local expression of inflammatory chemokines and induced rapid recruitment of circulating memory CD8(+) T cells. Anamnestic responses in front-line tissues are thus an integrated collaboration between front-line and circulating populations of memory CD8(+) T cells, and vaccines should establish both populations to maximize rapid responses.
authors.affiliation: Department of Microbiology, Center for Immunology, University of Minnesota Medical School, Minneapolis, Minnesota, USA.
authors.forename: Jason M
authors.initials: JM
authors.lastname: Schenkel
authors.forename: Kathryn A
authors.initials: KA
authors.lastname: Fraser
authors.forename: Vaiva
authors.initials: V
authors.lastname: Vezys
authors.forename: David
authors.initials: D
authors.lastname: Masopust
mesh_terms: D000818:Animals; D000956:Antigens, Viral / Q000276:immunology; D001117:Arenaviridae Infections / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D002465:Cell Movement / Q000276:immunology; D002478:Cells, Cultured; D005260:Female; D005836:Genitalia, Female / Q000276:immunology; D054884:Host-Pathogen Interactions; D007156:Immunologic Memory; D007371:Interferon-gamma / Q000235:genetics / Q000378:metabolism; D008213:Lymphocyte Activation; D008217:Lymphocytic choriomeningitis virus / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000235:genetics; D016176:T-Lymphocyte Subsets / Q000276:immunology*; D018183:Transplantation Chimera
chemical_list: D000956:Antigens, Viral; D016693:Receptors, Antigen, T-Cell, alpha-beta; D007371:Interferon-gamma
references.citation: Nat Med. 2010 May;16(5):558-64, 1p following 564
references.pmid: 20436484
references.citation: N Engl J Med. 2000 Oct 5;343(14):1020-34
references.pmid: 11018170
references.citation: Nature. 1999 Oct 14;401(6754):708-12
references.pmid: 10537110
references.citation: Science. 2008 Jan 11;319(5860):198-202
references.pmid: 18187654
references.citation: J Clin Invest. 2009 Jul;119(7):2062-73
references.pmid: 19546507
references.citation: Trends Immunol. 2013 Jan;34(1):27-32
references.pmid: 23036434
references.citation: Proc Natl Acad Sci U S A. 2010 Oct 19;107(42):17872-9
references.pmid: 20923878
references.citation: Nat Immunol. 2003 Sep;4(9):835-42
references.pmid: 12942084
references.citation: Nature. 2009 Nov 26;462(7272):510-3
references.pmid: 19898495
references.citation: J Immunol. 2008 Nov 1;181(9):5837-41
references.pmid: 18941171
references.citation: Nature. 2012 Feb 29;483(7388):227-31
references.pmid: 22388819
references.citation: Nat Immunol. 2003 Mar;4(3):225-34
references.pmid: 12563257
references.citation: Annu Rev Immunol. 2004;22:745-63
references.pmid: 15032595
references.citation: J Clin Invest. 2012 Dec;122(12):4606-20
references.pmid: 23143305
references.citation: Curr Opin Immunol. 2002 Feb;14(1):129-35
references.pmid: 11790543
references.citation: Nat Immunol. 2009 May;10(5):524-30
references.pmid: 19305395
references.citation: Science. 2001 Mar 23;291(5512):2413-7
references.pmid: 11264538
references.citation: J Immunol. 2011 Dec 1;187(11):5510-4
references.pmid: 22058417
references.citation: Nature. 2012 Nov 15;491(7424):463-7
references.pmid: 23075848
references.citation: J Clin Invest. 2010 Mar;120(3):907-23
references.pmid: 20197626
references.citation: Eur J Immunol. 2011 May;41(5):1192-5
references.pmid: 21469134
references.citation: J Exp Med. 2010 Mar 15;207(3):553-64
references.pmid: 20156972
references.citation: Proc Natl Acad Sci U S A. 2012 Nov 27;109(48):19739-44
references.pmid: 23150545
references.citation: J Immunol. 2012 May 15;188(10):4866-75
references.pmid: 22504644
references.citation: Cell. 2006 Feb 24;124(4):783-801
references.pmid: 16497588
references.citation: Nat Immunol. 2008 Sep;9(9):970-80
references.pmid: 18711434
references.citation: J Immunol. 2012 Jun 15;188(12):5811-7
references.pmid: 22675215
references.citation: Proc Natl Acad Sci U S A. 2011 Oct 4;108(40):16741-6
references.pmid: 21930933
references.citation: Immunity. 2008 Jun;28(6):859-69
references.pmid: 18499487
references.citation: Proc Natl Acad Sci U S A. 2012 May 1;109(18):7037-42
references.pmid: 22509047
references.citation: Mucosal Immunol. 2013 Jan;6(1):14-23
references.pmid: 23131785