title: Lung-resident memory CD8 T cells (TRM) are indispensable for optimal cross-protection against pulmonary virus infection.
abstract: Previous studies have shown that some respiratory virus infections leave local populations of tissue TRM cells in the lungs which disappear as heterosubtypic immunity declines. The location of these TRM cells and their contribution to the protective CTL response have not been clearly defined. Here, fluorescence microscopy is used to show that some CD103(+) TRM cells remain embedded in the walls of the large airways long after pulmonary immunization but are absent from systemically primed mice. Viral clearance from the lungs of the locally immunized mice precedes the development of a robust Teff response in the lungs. Whereas large numbers of virus-specific CTLs collect around the bronchial tree during viral clearance, there is little involvement of the remaining lung tissue. Much larger numbers of TEM cells enter the lungs of the systemically immunized animals but do not prevent extensive viral replication or damage to the alveoli. Together, these experiments show that virus-specific antibodies and TRM cells are both required for optimal heterosubtypic immunity, whereas circulating memory CD8 T cells do not substantially alter the course of disease.
authors.affiliation: 1.University of Connecticut Health Center, L3062, 263 Farmington Ave., Farmington, CT 06032, USA. lcauley@uchc.edu.
authors.forename: Tao
authors.initials: T
authors.lastname: Wu
authors.forename: Yinghong
authors.initials: Y
authors.lastname: Hu
authors.forename: Young-Tae
authors.initials: YT
authors.lastname: Lee
authors.forename: Keith R
authors.initials: KR
authors.lastname: Bouchard
authors.forename: Alexandre
authors.initials: A
authors.lastname: Benechet
authors.forename: Kamal
authors.initials: K
authors.lastname: Khanna
authors.forename: Linda S
authors.initials: LS
authors.lastname: Cauley
mesh_terms: D000818:Animals; D000914:Antibodies, Viral / Q000276:immunology; D015703:Antigens, CD / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D049109:Cell Proliferation; D056738:Cross Protection / Q000276:immunology*; D004285:Dogs; D007114:Immunization; D007156:Immunologic Memory; D009980:Influenza A virus / Q000276:immunology*; D039001:Integrin alpha Chains / Q000378:metabolism; D008168:Lung / Q000276:immunology* / Q000473:pathology / Q000821:virology*; D008213:Lymphocyte Activation / Q000276:immunology; D061985:Madin Darby Canine Kidney Cells; D051379:Mice; D009976:Orthomyxoviridae Infections / Q000276:immunology / Q000517:prevention & control* / Q000821:virology*; D010047:Ovalbumin / Q000276:immunology; D061026:Programmed Cell Death 1 Receptor / Q000378:metabolism; D013045:Species Specificity; D013997:Time Factors
chemical_list: D000914:Antibodies, Viral; D015703:Antigens, CD; D039001:Integrin alpha Chains; C491383:Pdcd1 protein, mouse; D061026:Programmed Cell Death 1 Receptor; C091367:alpha E integrins; D010047:Ovalbumin
keywords: cellular immunity; fluorescence microscopy; immunization; influenza virus