Abstract
IL-17 is regarded as a major effector cytokine with pro-inflammatory actions in autoimmune diseases. IL-17 has pleiotropic and environmental specific functions by promoting adaptive cytotoxic T-lymphocyte responses during inflammation. Therefore, it is tempting to speculate that IL-17 is important in inflammatory responses seen after organ transplantation. We determined IL-17 mRNA expression in the transplanted heart during early and late acute rejection episodes, and during immunological quiescence. Additionally, we analysed whether IL-17 is derived from graft-infiltrating lymphocytes. Endomyocardial biopsies (EMBs: n=41) from heart transplant recipients (n=29) who experienced an early (≤3 months) or late (>3 months) acute rejection episode or during an immunological quiescence period, were analysed for the presence of IL-17 mRNA. IL-17 production determined by flowcytometry was analysed in cultures of graft-infiltrating lymphocytes (GILs) derived from acute rejection (n=5) and non-rejection (n=5) EMBs stimulated with PMA and ionomycine. Twenty-two percent (9/41) of EMBs were positive for IL-17 mRNA. All (9/26) were observed in the early period after transplantation, while none (0/15) of the late biopsies expressed IL-17 mRNA (p=0.02). During early acute rejection, 56% (5/9) of the EMBs did express IL-17 mRNA, while EMBs from late acute rejections (0/5) did not express IL-17 mRNA (p=0.09). Only CD4+ cells from GIL cultures produced IL-17. In 60% of GIL cultures from acute rejection EMBs a significant proportion of CD4+ cells produced IL-17, while only one GIL culture from non-rejection EMBs contained CD4+IL-17+ cells. All CD4+IL-17+ cells expressed CD161, a cell surface expression marker of Th17 cells. CD8+ cells did not produce IL-17 neither expressed CD161. In conclusion, particularly early after heart transplantation IL-17 producing CD4+ T-cells home to the graft contributing to the acute rejection process.
Published Version
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