title: A Distinct Lung-Interstitium-Resident Memory CD8(+) T Cell Subset Confers Enhanced Protection to Lower Respiratory Tract Infection.
abstract: The nature and anatomic location of the protective memory CD8(+) T cell subset induced by intranasal vaccination remain poorly understood. We developed a vaccination model to assess the anatomic location of protective memory CD8(+) T cells and their role in lower airway infections. Memory CD8(+) T cells elicited by local intranasal, but not systemic, vaccination with an engineered non-replicative CD8(+) T cell-targeted antigen confer enhanced protection to a lethal respiratory viral challenge. This protection depends on a distinct CXCR3(LO) resident memory CD8(+) T (Trm) cell population that preferentially localizes to the pulmonary interstitium. Because they are positioned close to the mucosa, where infection occurs, interstitial Trm cells act before inflammation can recruit circulating memory CD8(+) T cells into the lung tissue. This results in a local protective immune response as early as 1 day post-infection. Hence, vaccine strategies that induce lung interstitial Trm cells may confer better protection against respiratory pathogens.
authors: Department of Veterans Affairs Tennessee Valley Healthcare System, Nashville, TN 37232, USA; Department of Pathology, Microbiology and Immunology, Vanderbilt University School of Medicine, Nashville, TN 37232, USA.
authors: Pavlo
authors: P
authors: Gilchuk
authors: Department of Pathology, Microbiology and Immunology, Vanderbilt University School of Medicine, Nashville, TN 37232, USA.
authors: Timothy M
authors: TM
authors: Hill
authors: Department of Immunology, St. Jude Children's Research Hospital, Memphis, TN 38105, USA.
authors: Clifford
authors: C
authors: Guy
authors: Department of Microbiology and Immunology, Emory University School of Medicine, Atlanta, GA 30322, USA.
authors: Sean R
authors: SR
authors: McMaster
authors: Department of Pathology, Microbiology and Immunology, Vanderbilt University School of Medicine, Nashville, TN 37232, USA.
authors: Kelli L
authors: KL
authors: Boyd
authors: Department of Pathology, Microbiology and Immunology, Vanderbilt University School of Medicine, Nashville, TN 37232, USA.
authors: Whitney A
authors: WA
authors: Rabacal
authors: Vanderbilt Technologies for Advanced Genomics Analyses and Research Design, Vanderbilt University School of Medicine, Nashville, TN 37232, USA; Department of Biostatistics, Vanderbilt University School of Medicine, Nashville, TN 37232, USA.
authors: Pengcheng
authors: P
authors: Lu
authors: Vanderbilt Technologies for Advanced Genomics Analyses and Research Design, Vanderbilt University School of Medicine, Nashville, TN 37232, USA.
authors: Yu
authors: Y
authors: Shyr
authors: Department of Microbiology and Immunology, Emory University School of Medicine, Atlanta, GA 30322, USA.
authors: Jacob E
authors: JE
authors: Kohlmeier
authors: Department of Pathology, Microbiology and Immunology, Vanderbilt University School of Medicine, Nashville, TN 37232, USA.
authors: Eric
authors: E
authors: Sebzda
authors: Department of Immunology, St. Jude Children's Research Hospital, Memphis, TN 38105, USA.
authors: Douglas R
authors: DR
authors: Green
authors: Department of Veterans Affairs Tennessee Valley Healthcare System, Nashville, TN 37232, USA; Department of Pathology, Microbiology and Immunology, Vanderbilt University School of Medicine, Nashville, TN 37232, USA. Electronic address: sebastian.joyce@vanderbilt.edu.
authors: Sebastian
authors: S
authors: Joyce
mesh_terms: D000281:Administration, Intranasal; D000595:Amino Acid Sequence; D000818:Animals; D000956:Antigens, Viral / Q000737:chemistry / Q000276:immunology*; D001835:Body Weight / Q000187:drug effects; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000821:virology; D015870:Gene Expression; D018928:Immunity, Mucosal / Q000187:drug effects; D007156:Immunologic Memory; D016130:Immunophenotyping; D008168:Lung / Q000187:drug effects / Q000276:immunology / Q000821:virology; D051379:Mice; D008822:Mice, Transgenic; D054367:Receptors, CXCR3 / Q000235:genetics / Q000276:immunology; D012141:Respiratory Tract Infections / Q000276:immunology / Q000473:pathology / Q000517:prevention & control* / Q000821:virology; D014611:Vaccination; D014615:Vaccinia / Q000276:immunology / Q000473:pathology / Q000517:prevention & control* / Q000821:virology; D014616:Vaccinia virus / Q000737:chemistry / Q000187:drug effects / Q000254:growth & development / Q000472:pathogenicity; D019562:Viral Load / Q000187:drug effects; D014765:Viral Vaccines / Q000008:administration & dosage* / Q000096:biosynthesis
chemical_list: D000956:Antigens, Viral; C515188:Cxcr3 protein, mouse; D054367:Receptors, CXCR3; D014765:Viral Vaccines