title: Lung transplant acceptance is facilitated by early events in the graft and is associated with lymphoid neogenesis.
abstract: Early immune responses are important in shaping long-term outcomes of human lung transplants. To examine the role of early immune responses in lung rejection and acceptance, we developed a method to retransplant mouse lungs. Retransplantation into T-cell-deficient hosts showed that for lungs and hearts alloimmune responses occurring within 72 h of transplantation are reversible. In contrast to hearts, a 72-h period of immunosuppression with costimulation blockade in primary allogeneic recipients suffices to prevent rejection of lungs upon retransplantation into untreated allogeneic hosts. Long-term lung acceptance is associated with induction of bronchus-associated lymphoid tissue, where Foxp3(+) cells accumulate and recipient T cells interact with CD11c(+) dendritic cells. Acceptance of retransplanted lung allografts is abrogated by treatment of immunosuppressed primary recipients with anti-CD25 antibodies. Thus, events contributing to lung transplant acceptance are established early in the graft and induction of bronchus-associated lymphoid tissue can be associated with an immune quiescent state.
authors.affiliation: Department of Surgery, Washington University in St Louis, St Louis, Missouri, USA.
authors.forename: W
authors.initials: W
authors.lastname: Li
authors.forename: A C
authors.initials: AC
authors.lastname: Bribriesco
authors.forename: R G
authors.initials: RG
authors.lastname: Nava
authors.forename: A A
authors.initials: AA
authors.lastname: Brescia
authors.forename: A
authors.initials: A
authors.lastname: Ibricevic
authors.forename: J H
authors.initials: JH
authors.lastname: Spahn
authors.forename: S L
authors.initials: SL
authors.lastname: Brody
authors.forename: J H
authors.initials: JH
authors.lastname: Ritter
authors.forename: A E
authors.initials: AE
authors.lastname: Gelman
authors.forename: A S
authors.initials: AS
authors.lastname: Krupnick
authors.forename: M J
authors.initials: MJ
authors.lastname: Miller
authors.forename: D
authors.initials: D
authors.lastname: Kreisel
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000008:administration & dosage; D039521:CD11c Antigen / Q000378:metabolism; D003713:Dendritic Cells / Q000187:drug effects / Q000276:immunology*; D051858:Forkhead Transcription Factors / Q000378:metabolism; D006085:Graft Survival / Q000187:drug effects; D006801:Humans; D007108:Immune Tolerance / Q000187:drug effects; D053645:Interleukin-2 Receptor alpha Subunit / Q000276:immunology; D016040:Lung Transplantation / Q000276:immunology*; D008212:Lymphocyte Depletion; D008221:Lymphoid Tissue / Q000187:drug effects / Q000254:growth & development / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008808:Mice, Inbred CBA; D023421:Models, Animal; D012086:Reoperation; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology*; D050378:T-Lymphocytes, Regulatory / Q000187:drug effects / Q000276:immunology*
chemical_list: D000911:Antibodies, Monoclonal; D039521:CD11c Antigen; D051858:Forkhead Transcription Factors; C498833:Foxp3 protein, mouse; D053645:Interleukin-2 Receptor alpha Subunit