Lung transplant acceptance is facilitated by early events in the graft and is associated with lymphoid neogenesis

W. Li, A. C. Bribriesco, R. G. Nava, A. A. Brescia, A. Ibricevic, J. H. Spahn, S. L. Brody, J. H. Ritter, A. E. Gelman, A. S. Krupnick, M. J. Miller, D. Kreisel

Research output: Contribution to journalArticlepeer-review

43 Scopus citations

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.

Original languageEnglish
Pages (from-to)544-554
Number of pages11
JournalMucosal Immunology
Volume5
Issue number5
DOIs
StatePublished - Sep 2012

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