Sequential evolution of IL-17 responses in the early period of allograft rejection

In addition to CD4⁺CD25⁺Foxp3⁺ regulatory T (Treg) cells which protect against autoimmune tissue injury, IL-17-producing CD4⁺ T (Th17) cells have been recently described and shown to play a crucial role in autoimmune injury. It appears that there is a reciprocal developmental pathway between Th17 and Treg cells. Although IL-17 is known to be associated with allograft rejection, the cellular source of IL-17 and the nature of Th17 in the context of allograft rejection remain unknown. In the current study, the dynamics of Treg and IL-17-producing cells after syngeneic and allogeneic transplantation were examined using a wild-type murine cardiac transplantation model. Ly6G⁺ cells were found to produce IL-17 during the early postoperative period and CD8⁺ as well as CD4⁺ T cells were also found to produce IL-17 during alloimmune response. Graft-infiltrating Ly6G⁺, CD4⁺, and even CD8⁺ cells were found to express IL-17 highly compared to those in spleen. Although the frequencies of Th17 and Treg were found to gradually increase in both syngeneic and allogeneic recipients, Th17/Treg ratios were significantly higher in recipients with allograft rejection than in syngeneic recipients. In conclusion, IL-17 is produced by neutrophils during the early postoperative period and subsequently by Th17 and CD8⁺ T cells during allograft rejection. Th17/Treg imbalance is associated with the development of allograft rejection. This study would provide basic information on Th17 biology for future investigation in the field of transplantation.