Potential Role of gamma delta T Cell-Derived IL-17 in Acute Cardiac Allograft Rejection

Abstract

Although aß T cells are known to participate in the development of acute cardiac allograft rejection, the role of ?d T cells remains poorly understood. We hypothesized that ?d T cells contribute to acute allograft rejection thru interleukin (IL)-17 production.Donor hearts from FVB mice (H-2q) were heterotopically transplanted into C57BL/6-wild type (WT) and ?d T cell-deficient (TCRd-/-) recipient mice (H-2b). Overall graft survival was monitored. Graft infiltrating cell profile, including ?d 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.Graft survival was prolonged in TCRd-/- recipients compared with WT controls. Graft infiltrating cells, including CD45+, CD4+, CD8+, and Gr1+ cells were significantly decreased in TCRd-/- recipients compared with WT. Donor hearts transplanted into TCRd-/- 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 TCRd-/- recipients. Finally, V?1+ and V?4+ T cells did not produce IL-17, although both represent 20% to 30% total graft infiltrating ?d T cells.The ?d T cells promote acute cardiac allograft rejection, presumably by producing IL-17. The ?d T cell depletion may prove beneficial in prolonging allograft survival by suppressing IL-17 production.

View details for DOI 10.1016/j.athoracsur.2012.03.049

View details for Web of Science ID 000306700100040

View details for PubMedID 22560321