title: Functional classification of memory CD8(+) T cells by CX3CR1 expression.
abstract: Localization of memory CD8(+) T cells to lymphoid or peripheral tissues is believed to correlate with proliferative capacity or effector function. Here we demonstrate that the fractalkine-receptor/CX3CR1 distinguishes memory CD8(+) T cells with cytotoxic effector function from those with proliferative capacity, independent of tissue-homing properties. CX3CR1-based transcriptome and proteome-profiling defines a core signature of memory CD8(+) T cells with effector function. We find CD62L(hi)CX3CR1(+) memory T cells that reside within lymph nodes. This population shows distinct migration patterns and positioning in proximity to pathogen entry sites. Virus-specific CX3CR1(+) memory CD8(+) T cells are scarce during chronic infection in humans and mice but increase when infection is controlled spontaneously or by therapeutic intervention. This CX3CR1-based functional classification will help to resolve the principles of protective CD8(+) T-cell memory.
authors.affiliation: Institute of Experimental Immunology, Universitätsklinikum Bonn, Sigmund-Freud-Street 25, Bonn 53105, Germany.
authors.forename: Jan P
authors.initials: JP
authors.lastname: Böttcher
authors.affiliation: Genomics and Immunoregulation, LIMES-Institute, Universität Bonn, Carl-Troll-Street 31, Bonn 53115, Germany.
authors.forename: Marc
authors.identifier: http://orcid.org/0000-0001-9704-148X
authors.initials: M
authors.lastname: Beyer
authors.affiliation: Max Planck Institute of Biochemistry, Am Klopferspitz 18, München 82152, Germany.
authors.forename: Felix
authors.identifier: http://orcid.org/0000-0003-1000-7989
authors.initials: F
authors.lastname: Meissner
authors.affiliation: Institute of Experimental Immunology, Universitätsklinikum Bonn, Sigmund-Freud-Street 25, Bonn 53105, Germany.
authors.forename: Zeinab
authors.initials: Z
authors.lastname: Abdullah
authors.affiliation: Genomics and Immunoregulation, LIMES-Institute, Universität Bonn, Carl-Troll-Street 31, Bonn 53115, Germany.
authors.forename: Jil
authors.initials: J
authors.lastname: Sander
authors.affiliation: Institute of Molecular Immunology and Experimental Oncology, Technische Universität München, Ismaninger Street 22, München 81675, Germany.
authors.forename: Bastian
authors.initials: B
authors.lastname: Höchst
authors.affiliation: Institute of Experimental Immunology, Universitätsklinikum Bonn, Sigmund-Freud-Street 25, Bonn 53105, Germany.
authors.forename: Sarah
authors.initials: S
authors.lastname: Eickhoff
authors.affiliation: Max Planck Institute of Biochemistry, Am Klopferspitz 18, München 82152, Germany.
authors.forename: Jan C
authors.initials: JC
authors.lastname: Rieckmann
authors.affiliation: Institute of Virology, Technische Universität München, Troger Street 30, München 81675, Germany.
authors.forename: Caroline
authors.initials: C
authors.lastname: Russo
authors.affiliation: Institute of Virology, Technische Universität München, Troger Street 30, München 81675, Germany.
authors.forename: Tanja
authors.initials: T
authors.lastname: Bauer
authors.affiliation: Clinic for Internal Medicine II, Universitätsklinikum Freiburg, Hugstetter Street 55, Freiburg 79106, Germany.
authors.forename: Tobias
authors.initials: T
authors.lastname: Flecken
authors.affiliation: Clinic for Internal Medicine II, Universitätsklinikum Freiburg, Hugstetter Street 55, Freiburg 79106, Germany.
authors.forename: Dominik
authors.initials: D
authors.lastname: Giesen
authors.affiliation: Institute of Experimental Immunology, Universitätsklinikum Bonn, Sigmund-Freud-Street 25, Bonn 53105, Germany.
authors.forename: Daniel
authors.initials: D
authors.lastname: Engel
authors.affiliation: Weizmann Institute of Science, Rehovot 76100, Israel.
authors.forename: Steffen
authors.initials: S
authors.lastname: Jung
authors.affiliation: Institute of Microbiology, Immunology and Hygiene, Technische Universität München, Troger Street 30, München 81675, Germany.
authors.forename: Dirk H
authors.initials: DH
authors.lastname: Busch
authors.affiliation: Institute of Virology, Technische Universität München, Troger Street 30, München 81675, Germany.
authors.forename: Ulrike
authors.initials: U
authors.lastname: Protzer
authors.affiliation: Clinic for Internal Medicine II, Universitätsklinikum Freiburg, Hugstetter Street 55, Freiburg 79106, Germany.
authors.forename: Robert
authors.initials: R
authors.lastname: Thimme
authors.affiliation: Max Planck Institute of Biochemistry, Am Klopferspitz 18, München 82152, Germany.
authors.forename: Matthias
authors.initials: M
authors.lastname: Mann
authors.affiliation: Institute of Experimental Immunology, Universitätsklinikum Bonn, Sigmund-Freud-Street 25, Bonn 53105, Germany.
authors.forename: Christian
authors.initials: C
authors.lastname: Kurts
authors.affiliation: Genomics and Immunoregulation, LIMES-Institute, Universität Bonn, Carl-Troll-Street 31, Bonn 53115, Germany.
authors.forename: Joachim L
authors.initials: JL
authors.lastname: Schultze
authors.affiliation: Institute of Experimental Immunology, Universitätsklinikum Bonn, Sigmund-Freud-Street 25, Bonn 53105, Germany.
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Kastenmüller
authors.affiliation: Institute of Experimental Immunology, Universitätsklinikum Bonn, Sigmund-Freud-Street 25, Bonn 53105, Germany.|Institute of Molecular Immunology and Experimental Oncology, Technische Universität München, Ismaninger Street 22, München 81675, Germany.
authors.forename: Percy A
authors.initials: PA
authors.lastname: Knolle
mesh_terms: D000257:Adenoviridae Infections / Q000276:immunology; D000818:Animals; D001117:Arenaviridae Infections / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000145:classification / Q000276:immunology; D000073883:CX3C Chemokine Receptor 1; D049109:Cell Proliferation; D002853:Chromatography, Liquid; D005434:Flow Cytometry; D020869:Gene Expression Profiling; D006801:Humans; D008088:Listeriosis / Q000276:immunology; D008217:Lymphocytic choriomeningitis virus; D051379:Mice; D019707:Receptors, Chemokine / Q000276:immunology*; D017423:Sequence Analysis, RNA; D016176:T-Lymphocyte Subsets / Q000145:classification / Q000276:immunology*; D013602:T-Lymphocytes, Cytotoxic / Q000145:classification / Q000276:immunology*; D053719:Tandem Mass Spectrometry
chemical_list: D000073883:CX3C Chemokine Receptor 1; C095235:CX3CR1 protein, human; C471885:Cx3cr1 protein, mouse; D019707:Receptors, Chemokine