| 초록 |
Background: Previously reports showed that CCR7+CD8+ T cells have suppressive effect on various pathogenic immune cells. The aim of this study is to investigate the regulatory function of CCR7+CD8+ T cells on allo-reactive effector T cells involved in acute rejection in kidney transplantation.
Methods: We investigated the suppressive effect of CCR7+CD8+ T cells on T cell proliferation and also inflammatory cytokine induced injury on human primary renal tubular epithelial cells (HPRTEpiC) by FACs analysis and ELISA. Also, we compared the proportion of CCR7+CD8+ T cells in peripheral blood mononuclear cells by FACs analysis between biopsy proven acute rejection (AR)(n=22) and biopsy proven normal histology (NC)(n=16).
Results: CCR7+CD8+ T cells significantly decreased the proportion of IFN-g, IL-17/CD4+T cells, and production of IL-17 and IL-2 (P<0.05 for each). In contrast, CCR7+CD8+ T cells increased the production of IL-10/CD4+T cells compared to Th17 condition. Second, CCR7+CD8+ T cells significantly reduced IL-6, IL-8 and CCL20 secretion from HPRTEpiC, which have been induced by inflammatory cytokines or activated T cells. Also, Our results showed that CCR7+CD8+ T cells significantly reduced IL-17, IFN-g and IL-2 production from T cells co-cultured with HPRTEpiC. Third, ex vivo analysis of PBMCs isolated from kidney transplant recipients (KTRs) with or without acute rejection, the percentage of CCR7+CD8+ T cells showed significant decrease in the AR group compared to NC group (P<0.05). In contrast, the percentage of CD28nullCD57+ T cell and effector memory CD8 T cell (CD8+TEMRA) increased in the AR group compared to NC group. In peripheral blood from total patients groups, CCR7+CD8+ T cells was inversely correlated with the CD28nullCD57+ T cell and effector memory CD8 T cell (CD8+TEMRA).
Conclusion: This study showed that the CCR7+CD8+ T cells effectively regulate effector T cells associated with allograft rejection. It suggests that use of CCR7+CD8+ T cells may be proposed as therapeutic strategy to improve allograft outcome. |