title: Tissue-specific programming of memory CD8 T cell subsets impacts protection against lethal respiratory virus infection.
abstract: How tissue-specific anatomical distribution and phenotypic specialization are linked to protective efficacy of memory T cells against reinfection is unclear. Here, we show that lung environmental cues program recently recruited central-like memory cells with migratory potentials for their tissue-specific functions during lethal respiratory virus infection. After entering the lung, some central-like cells retain their original CD27hiCXCR3hiphenotype, enabling them to localize near the infected bronchiolar epithelium and airway lumen to function as the first line of defense against pathogen encounter. Others, in response to local cytokine triggers, undergo a secondary program of differentiation that leads to the loss of CXCR3, migration arrest, and clustering within peribronchoarterial areas and in interalveolar septa. Here, the immune system adapts its response to prevent systemic viral dissemination and mortality. These results reveal the striking and unexpected spatial organization of central- versus effector-like memory cells within the lung and how cooperation between these two subsets contributes to host defense.
authors.affiliation: Department of Pathology, Immunology, and Laboratory Medicine, University of Florida, Gainesville, FL 32611.
authors.forename: Georges
authors.identifier: 0000-0003-0353-2515
authors.initials: G
authors.lastname: Abboud
authors.affiliation: Department of Pathology, Immunology, and Laboratory Medicine, University of Florida, Gainesville, FL 32611.
authors.forename: Pritesh
authors.identifier: 0000-0002-4697-9475
authors.initials: P
authors.lastname: Desai
authors.affiliation: Department of Pathology, Immunology, and Laboratory Medicine, University of Florida, Gainesville, FL 32611.
authors.forename: Farhad
authors.identifier: 0000-0003-0665-0824
authors.initials: F
authors.lastname: Dastmalchi
authors.affiliation: Department of Pathology, Immunology, and Laboratory Medicine, University of Florida, Gainesville, FL 32611.
authors.forename: Jessica
authors.identifier: 0000-0003-4543-1392
authors.initials: J
authors.lastname: Stanfield
authors.affiliation: Department of Pathology, Immunology, and Laboratory Medicine, University of Florida, Gainesville, FL 32611.
authors.forename: Vikas
authors.initials: V
authors.lastname: Tahiliani
authors.affiliation: Department of Pathology, Immunology, and Laboratory Medicine, University of Florida, Gainesville, FL 32611.
authors.forename: Tarun E
authors.identifier: 0000-0002-9175-7222
authors.initials: TE
authors.lastname: Hutchinson
authors.affiliation: Department of Pathology, Immunology, and Laboratory Medicine, University of Florida, Gainesville, FL 32611 ssalek@ufl.edu.
authors.forename: Shahram
authors.identifier: 0000-0002-2336-8452
authors.initials: S
authors.lastname: Salek-Ardakani
mesh_terms: D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000473:pathology; D005260:Female; D007156:Immunologic Memory; D051379:Mice; D008822:Mice, Transgenic; D011650:Pulmonary Alveoli / Q000276:immunology* / Q000473:pathology; D012141:Respiratory Tract Infections / Q000235:genetics / Q000276:immunology* / Q000473:pathology / Q000821:virology; D018108:Respirovirus / Q000276:immunology*; D010253:Respirovirus Infections / Q000235:genetics / Q000276:immunology* / Q000473:pathology