title: Polarized alloantigen presentation by airway epithelial cells contributes to direct CD8+ T cell activation in the airway.
abstract: Activated T lymphocytes are abundant in the airway during lung allograft rejection. Based on respiratory viral studies, it is the current paradigm that T cells cannot divide in the airway, and that their accumulation in the lumen of the respiratory tract is the exclusive result of recruitment from other sites, such as mediastinal lymph nodes. Here, we show that CD8(+) T cell activation and proliferation can occur in the airway after orthotopic lung transplantation. We also demonstrate that airway epithelium expresses major histocompatibility class I predominantly on the apical surface, both in vitro and in vivo, and initiates CD8(+) T cell responses in a polarized fashion, favoring luminal activation. Our data identify a unique site for CD8(+) T cell activation after lung transplantation, and suggest that attenuating these responses may provide a clinically relevant target.
authors.affiliation: Department of Surgery, Washington University in St. Louis, St. Louis, Missouri 63110-1013, USA.
authors.forename: Daniel
authors.initials: D
authors.lastname: Kreisel
authors.forename: Jiaming
authors.initials: J
authors.lastname: Lai
authors.forename: Steven B
authors.initials: SB
authors.lastname: Richardson
authors.forename: Aida
authors.initials: A
authors.lastname: Ibricevic
authors.forename: Ruben G
authors.initials: RG
authors.lastname: Nava
authors.forename: Xue
authors.initials: X
authors.lastname: Lin
authors.forename: Wenjun
authors.initials: W
authors.lastname: Li
authors.forename: Christopher G
authors.initials: CG
authors.lastname: Kornfeld
authors.forename: Mark J
authors.initials: MJ
authors.lastname: Miller
authors.forename: Steven L
authors.initials: SL
authors.lastname: Brody
authors.forename: Andrew E
authors.initials: AE
authors.lastname: Gelman
authors.forename: Alexander S
authors.initials: AS
authors.lastname: Krupnick
mesh_terms: D000818:Animals; D016026:Bone Marrow Transplantation / Q000379:methods; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D049109:Cell Proliferation; D004847:Epithelial Cells / Q000378:metabolism*; D005434:Flow Cytometry / Q000379:methods; D005805:Genes, MHC Class I; D007519:Isoantigens / Q000276:immunology* / Q000378:metabolism; D008168:Lung / Q000473:pathology; D016040:Lung Transplantation / Q000379:methods; D008213:Lymphocyte Activation; D051379:Mice; D008810:Mice, Inbred C57BL; D008808:Mice, Inbred CBA; D008819:Mice, Nude; D014132:Trachea / Q000276:immunology* / Q000378:metabolism
chemical_list: D007519:Isoantigens