Role of Passenger Leukocytes in Allograft Rejection: Effect of Depletion of Donor Alveolar Macrophages on the Local Production of TNF-α, T Helper 1/T Helper 2 Cytokines, IgG Subclasses, and Pathology in a Rat Model of Lung Transplantation

Yasuo Sekine, Linda K. Bowen, Kathleen M. Heidler, Nico Van Rooijen, John W. Brown, Oscar W. Cummings, David S. Wilkes

Research output: Contribution to journalArticle

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Acute lung allograft rejection is believed to be initiated by passenger leukocytes, such as alveolar macrophages (AM), in the donor organ, which release TNF-α, and present alloantigens to host lymphocytes, leading to up-regulated Th1 cellular and humoral immunity. However, the role of donor AM in local TNF-α synthesis, and their ability to induce local Th1 cellular and humoral immunity have not been evaluated. By depleting Brown Norway (BN, RT1n) rat lung allografts of AM before transplantation into Lewis rat (LEW, RT11) recipients, the current study determined the role of donor AM in inducing the production of TNF-α, IFN-γ (Th1 cytokine), IL-4 (Th2 cytokine), IgG subtypes, and rejection pathology in the allograft. The data show that compared with untreated BN allografts, pretransplant depletion of donor lung AM resulted in significantly less TNF-α, and IFN-γ production in allograft bronchoalveolar lavage fluid with variable effects on local IL-4 production. Depletion of AM in the donor lung before transplantation affected the local production of several IgG subclasses. However, pretransplant depletion of donor AM had no effect on the development of the pathology of severe acute rejection. These data show that donor AM have a central role in the local synthesis of TNF-α and induce the production of IFN-γ and IgG subtypes, locally, during acute lung allograft rejection. However, depletion of AM before transplantation does not prevent the development of severe acute rejection in BN rat lungs transplanted into LEW recipients.

Original languageEnglish (US)
Pages (from-to)4084-4093
Number of pages10
JournalJournal of Immunology
Issue number8
StatePublished - Oct 15 1997


ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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