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

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.