title: Alpha E beta 7 (CD103) expression identifies a highly active, tonsil-resident effector-memory CTL population.
abstract: The characterization of antiviral CTL responses has largely been limited to assessing Ag-specific immune responses in the peripheral blood. Consequently, there is an incomplete understanding of the cellular immune responses at mucosal sites where many viruses enter and initially replicate and how the Ag specificity and activation status of CTL derived from these mucosal sites may differ from that of blood-derived CTL. In this study, we show that EBV-specific CTL responses in the tonsils are of comparable specificity and breadth but of a significantly higher magnitude compared with responses in the peripheral blood. EBV-specific, tonsil-resident, but not PBMC-derived, T cells expressed the integrin/activation marker CD103 (alphaEbeta7), consistent with the detection of its ligand, E-cadherin, on tonsillar squamous cells. These CD8-positive, CD103-positive, tonsil-derived CTL were largely CCR7- and CD45RA- negative effector-memory cells and responded to lower Ag concentrations in in vitro assays than their CD103-negative PBMC-derived counterparts. Thus, EBV-specific CTL in the tonsil, a crucial site for EBV entry and replication, are of greater magnitude and phenotypically distinct from CTL in the peripheral blood and may be important for effective control of this orally transmitted virus.
authors.affiliation: Partners AIDS Research Center, Massachusetts General Hospital, Boston 02129, USA.
authors.forename: Tonia
authors.initials: T
authors.lastname: Woodberry
authors.forename: Todd J
authors.initials: TJ
authors.lastname: Suscovich
authors.forename: Leah M
authors.initials: LM
authors.lastname: Henry
authors.forename: Meredith
authors.initials: M
authors.lastname: August
authors.forename: Michael T
authors.initials: MT
authors.lastname: Waring
authors.forename: Amitinder
authors.initials: A
authors.lastname: Kaur
authors.forename: Christoph
authors.initials: C
authors.lastname: Hess
authors.forename: Jeffery L
authors.initials: JL
authors.lastname: Kutok
authors.forename: Jon C
authors.initials: JC
authors.lastname: Aster
authors.forename: Frederick
authors.initials: F
authors.lastname: Wang
authors.forename: David T
authors.initials: DT
authors.lastname: Scadden
authors.forename: Christian
authors.initials: C
authors.lastname: Brander
mesh_terms: D000956:Antigens, Viral / Q000276:immunology; D015820:Cadherins / Q000096:biosynthesis / Q000235:genetics; D018984:Epitopes, T-Lymphocyte / Q000276:immunology; D020031:Epstein-Barr Virus Infections / Q000276:immunology; D004854:Herpesvirus 4, Human / Q000276:immunology; D006801:Humans; D007150:Immunohistochemistry; D007156:Immunologic Memory / Q000276:immunology* / Q000502:physiology; D016023:Integrins / Q000096:biosynthesis* / Q000235:genetics; D008024:Ligands; D014066:Palatine Tonsil / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology* / Q000378:metabolism
chemical_list: D000956:Antigens, Viral; D015820:Cadherins; D018984:Epitopes, T-Lymphocyte; D016023:Integrins; D008024:Ligands; C070709:integrin alphaEbeta7