title: Cutting edge: Pseudomonas aeruginosa abolishes established lung transplant tolerance by stimulating B7 expression on neutrophils.
abstract: The mechanisms that link bacterial infection to solid organ rejection remain unclear. In this study, we show that following the establishment of lung allograft acceptance in mice, Pseudomonas aeruginosa airway infection induces a G-CSF-dependent neutrophilia that stimulates acute rejection. Graft-infiltrating neutrophils sharply upregulate the B7 molecules CD80 and CD86, but they do not express CD40 or MHC class II in response to P. aeruginosa infection. Neutrophil B7 promotes naive CD4(+) T cell activation and intragraft IL-2(+), IFN-γ(+), and IL-17(+) T lymphocyte accumulation. Intravital two-photon microscopy reveals direct interactions between neutrophils and CD4(+) T cells within pulmonary allografts. Importantly, lung rejection in P. aeruginosa-infected recipients is triggered by CD80/86 on neutrophils and can be prevented by B7 blockade without affecting clearance of this pathogen. These data show that neutrophils enhance T cell activation through B7 trans-costimulation and suggest that inhibiting neutrophil-mediated alloimmunity can be accomplished without compromising bacterial immune surveillance.
authors.affiliation: Department of Surgery, Washington University School of Medicine, St. Louis, MO 63110, USA.
authors.forename: Sumiharu
authors.initials: S
authors.lastname: Yamamoto
authors.forename: Ruben G
authors.initials: RG
authors.lastname: Nava
authors.forename: Jihong
authors.initials: J
authors.lastname: Zhu
authors.forename: Howard J
authors.initials: HJ
authors.lastname: Huang
authors.forename: Mohsen
authors.initials: M
authors.lastname: Ibrahim
authors.forename: Thalachallour
authors.initials: T
authors.lastname: Mohanakumar
authors.forename: Mark J
authors.initials: MJ
authors.lastname: Miller
authors.forename: Alexander S
authors.initials: AS
authors.lastname: Krupnick
authors.forename: Daniel
authors.initials: D
authors.lastname: Kreisel
authors.forename: Andrew E
authors.initials: AE
authors.lastname: Gelman
mesh_terms: D000818:Animals; D018122:B7-1 Antigen / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D006084:Graft Rejection / Q000209:etiology* / Q000276:immunology / Q000382:microbiology; D016040:Lung Transplantation / Q000009:adverse effects*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009504:Neutrophils / Q000276:immunology* / Q000378:metabolism / Q000382:microbiology*; D011552:Pseudomonas Infections / Q000150:complications / Q000276:immunology* / Q000382:microbiology; D023001:Transplantation Tolerance / Q000276:immunology*; D015854:Up-Regulation / Q000276:immunology*
chemical_list: D018122:B7-1 Antigen