Anti-type V collagen lymphocytes that express IL-17 and IL-23 induce rejection pathology in fresh and well-healed lung transplants

S. Yoshida, A. Haque, T. Mizobuchi, T. Iwata, M. Chiyo, T. J. Webb, L. A. Baldridge, K. M. Heidler, O. W. Cummings, T. Fujisawa, J. S. Blum, D. D. Brand, D. S. Wilkes

Research output: Contribution to journalArticle

142 Scopus citations

Abstract

Immunity to collagen V [col(V)] contributes to lung 'rejection.' We hypothesized that ischemia reperfusion injury (IRI) associated with lung transplantation unmasks antigenic col(V) such that fresh and well-healed lung grafts have differential susceptibility to anti-col(V)-mediated injury; and expression of the autoimmune cytokines, IL-17 and IL-23, are associated with this process. Adoptive transfer of col(V)-reactive lymphocytes to WKY rats induced grade 2 rejection in fresh isografts, but induced worse pathology (grade 3) when transferred to isograft recipients 30 days post-transplantation. Immunhistochemistry detected col(V) in fresh and well-healed isografts but not native lungs. Hen egg lysozyme-reactive lymphocytes (HEL, control) did not induce lung disease in any group. Col(V), but not HEL, immunization induced transcripts for IL-17 and IL-23 (p19) in the cells utilized for adoptive transfer. Transcripts for IL-17 were upregulated in fresh, but not well-healed isografts after transfer of col(V)-reactive cells. These data show that IRI predisposes to anti-col(V)-mediated pathology; col(V)-reactive lymphocytes express IL-17 and IL-23; and anti-col(V)-mediated lung disease is associated with local expression of IL-17. Finally, because of similar histologic patterns, the pathology of clinical rejection may reflect the activity of autoimmunity to col(V) and/or alloimmunity.

Original languageEnglish (US)
Pages (from-to)724-735
Number of pages12
JournalAmerican Journal of Transplantation
Volume6
Issue number4
DOIs
StatePublished - Apr 2006

Keywords

  • Autoimmunity
  • Graft rejection
  • Lung transplantation
  • Type V collagen

ASJC Scopus subject areas

  • Immunology

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    Yoshida, S., Haque, A., Mizobuchi, T., Iwata, T., Chiyo, M., Webb, T. J., Baldridge, L. A., Heidler, K. M., Cummings, O. W., Fujisawa, T., Blum, J. S., Brand, D. D., & Wilkes, D. S. (2006). Anti-type V collagen lymphocytes that express IL-17 and IL-23 induce rejection pathology in fresh and well-healed lung transplants. American Journal of Transplantation, 6(4), 724-735. https://doi.org/10.1111/j.1600-6143.2006.01236.x