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

Mucosal Immunol. 2012 Sep;5(5):544-54. doi: 10.1038/mi.2012.30. Epub 2012 May 2.


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.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Antibodies, Monoclonal / administration & dosage
  • CD11c Antigen / metabolism
  • Dendritic Cells / drug effects
  • Dendritic Cells / immunology*
  • Forkhead Transcription Factors / metabolism
  • Graft Survival / drug effects
  • Humans
  • Immune Tolerance / drug effects
  • Interleukin-2 Receptor alpha Subunit / immunology
  • Lung Transplantation / immunology*
  • Lymphocyte Depletion
  • Lymphoid Tissue / drug effects
  • Lymphoid Tissue / growth & development
  • Lymphoid Tissue / immunology*
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred C57BL
  • Mice, Inbred CBA
  • Models, Animal
  • Reoperation
  • T-Lymphocytes / drug effects
  • T-Lymphocytes / immunology*
  • T-Lymphocytes, Regulatory / drug effects
  • T-Lymphocytes, Regulatory / immunology*


  • Antibodies, Monoclonal
  • CD11c Antigen
  • Forkhead Transcription Factors
  • Foxp3 protein, mouse
  • Interleukin-2 Receptor alpha Subunit