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

Background. Although alpha beta T cells are known to participate in the development of acute cardiac allograft rejection, the role of gamma delta T cells remains poorly understood. We hypothesized that gamma delta 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 gamma delta T cell-deficient (TCR delta(-/-)) recipient mice (H-2(b)). Overall graft survival was monitored. Graft infiltrating cell profile, including gamma delta 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 TCR delta(-/-) recipients compared with WT controls. Graft infiltrating cells, including CD45(+), CD4(+), CD8(+), and Gr1(+) cells were significantly decreased in TCR delta(-/-) recipients compared with WT. Donor hearts transplanted into TCR delta(-/-) 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 TCR delta(-/-) recipients. Finally, V gamma 1(+) and V gamma 4(+) T cells did not produce IL-17, although both represent 20% to 30% total graft infiltrating gamma delta T cells. Conclusions. The gamma delta T cells promote acute cardiac allograft rejection, presumably by producing IL-17. The gamma delta T cell depletion may prove beneficial in prolonging allograft survival by suppressing IL-17 production. (Ann Thorac Surg 2012;94:542-8) (c) 2012 by The Society of Thoracic Surgeons