title: Tissue reservoirs of antiviral T cell immunity in persistent human CMV infection.
abstract: T cell responses to viruses are initiated and maintained in tissue sites; however, knowledge of human antiviral T cells is largely derived from blood. Cytomegalovirus (CMV) persists in most humans, requires T cell immunity to control, yet tissue immune responses remain undefined. Here, we investigated human CMV-specific T cells, virus persistence and CMV-associated T cell homeostasis in blood, lymphoid, mucosal and secretory tissues of 44 CMV seropositive and 28 seronegative donors. CMV-specific T cells were maintained in distinct distribution patterns, highest in blood, bone marrow (BM), or lymph nodes (LN), with the frequency and function in blood distinct from tissues. CMV genomes were detected predominantly in lung and also in spleen, BM, blood and LN. High frequencies of activated CMV-specific T cells were found in blood and BM samples with low virus detection, whereas in lung, CMV-specific T cells were present along with detectable virus. In LNs, CMV-specific T cells exhibited quiescent phenotypes independent of virus. Overall, T cell differentiation was enhanced in sites of viral persistence with age. Together, our results suggest tissue T cell reservoirs for CMV control shaped by both viral and tissue-intrinsic factors, with global effects on homeostasis of tissue T cells over the lifespan.
authors.affiliation: Columbia Center for Translational Immunology, Columbia University Medical Center, New York, NY 10032.|Department of Medicine, Columbia University Medical Center, New York, NY 10032.
authors.forename: Claire L
authors.initials: CL
authors.lastname: Gordon
authors.affiliation: Columbia Center for Translational Immunology, Columbia University Medical Center, New York, NY 10032.|Department of Microbiology and Immunology, Columbia University Medical Center, New York, NY 10032.
authors.forename: Michelle
authors.identifier: 0000-0002-2593-3857
authors.initials: M
authors.lastname: Miron
authors.affiliation: Columbia Center for Translational Immunology, Columbia University Medical Center, New York, NY 10032.|Department of Microbiology and Immunology, Columbia University Medical Center, New York, NY 10032.
authors.forename: Joseph J C
authors.initials: JJ
authors.lastname: Thome
authors.affiliation: Columbia Center for Translational Immunology, Columbia University Medical Center, New York, NY 10032.
authors.forename: Nobuhide
authors.identifier: 0000-0002-1217-6842
authors.initials: N
authors.lastname: Matsuoka
authors.affiliation: Columbia Center for Translational Immunology, Columbia University Medical Center, New York, NY 10032.
authors.forename: Joshua
authors.identifier: 0000-0003-3780-1875
authors.initials: J
authors.lastname: Weiner
authors.affiliation: Department of Immunobiology, University of Arizona, Tucson, AZ 85721.
authors.forename: Michael A
authors.identifier: 0000-0003-0010-7935
authors.initials: MA
authors.lastname: Rak
authors.affiliation: Department of Immunobiology, University of Arizona, Tucson, AZ 85721.
authors.forename: Suzu
authors.initials: S
authors.lastname: Igarashi
authors.affiliation: Columbia Center for Translational Immunology, Columbia University Medical Center, New York, NY 10032.
authors.forename: Tomer
authors.identifier: 0000-0003-2899-904X
authors.initials: T
authors.lastname: Granot
authors.affiliation: LiveOnNY, New York, NY 10001.
authors.forename: Harvey
authors.identifier: 0000-0002-1857-5190
authors.initials: H
authors.lastname: Lerner
authors.affiliation: Department of Immunobiology, University of Arizona, Tucson, AZ 85721.
authors.forename: Felicia
authors.identifier: 0000-0002-6646-7290
authors.initials: F
authors.lastname: Goodrum
authors.affiliation: Columbia Center for Translational Immunology, Columbia University Medical Center, New York, NY 10032 df2396@cumc.columbia.edu.|Department of Microbiology and Immunology, Columbia University Medical Center, New York, NY 10032.|Department of Surgery, Columbia University Medical Center, New York, NY 10032.
authors.forename: Donna L
authors.identifier: 0000-0001-8236-9183
authors.initials: DL
authors.lastname: Farber
mesh_terms: D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D003587:Cytomegalovirus / Q000276:immunology; D003586:Cytomegalovirus Infections / Q000276:immunology*; D006801:Humans; D007371:Interferon-gamma / Q000096:biosynthesis; D008198:Lymph Nodes / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology*; D014766:Viremia / Q000276:immunology
chemical_list: D007371:Interferon-gamma