Potential role of γδ T cell-derived IL-17 in acute cardiac allograft rejection

Naoyuki Kimura, Susumu Nakae, Satoshi Itoh, Denis R. Merk, Xi Wang, Yongquan Gong, Homare Okamura, Paul A. Chang, Hideo Adachi, Robert C. Robbins, Michael P. Fischbein

Research output: Contribution to journalArticlepeer-review

14 Scopus citations

Abstract

Background: Although αβ T cells are known to participate in the development of acute cardiac allograft rejection, the role of γδ T cells remains poorly understood. We hypothesized that γδ T cells contribute to acute allograft rejection thru interleukin (IL)-17 production. Methods: Donor hearts from FVB mice (H-2 q) were heterotopically transplanted into C57BL/6-wild type (WT) and γδ T cell-deficient (TCRδ -/-) recipient mice (H-2 b). Overall graft survival was monitored. Graft infiltrating cell profile, including γδ T cell subtype, cytokine expression, and myeloperoxidase activity were measured by flow cytometry, TaqMan (Applied Biosystems, Carlsbad, CA) polymerase chain reaction, and myeloperoxidase assay, respectively, on postoperative days 3 and 6. Results: Graft survival was prolonged in TCRδ -/- recipients compared with WT controls. Graft infiltrating cells, including CD45 +, CD4 +, CD8 +, and Gr1 + cells were significantly decreased in TCRδ -/- recipients compared with WT. Donor hearts transplanted into TCRδ -/- recipients had reduced IL-17 and IL-6 messenger RNA expression. Corroborating the gene expression, intracellular cytokine staining showed decreased IL-17 producing cells in TCRδ -/- recipients. Finally, Vγ1 + and Vγ4 + T cells did not produce IL-17, although both represent 20% to 30% total graft infiltrating γδ T cells. Conclusions: The γδ T cells promote acute cardiac allograft rejection, presumably by producing IL-17. The γδ T cell depletion may prove beneficial in prolonging allograft survival by suppressing IL-17 production.

Original languageEnglish (US)
Pages (from-to)542-548
Number of pages7
JournalAnnals of Thoracic Surgery
Volume94
Issue number2
DOIs
StatePublished - Aug 2012
Externally publishedYes

ASJC Scopus subject areas

  • Surgery
  • Pulmonary and Respiratory Medicine
  • Cardiology and Cardiovascular Medicine

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