Dysregulation of Th17 cells during the early post-transplant period in patients under calcineurin inhibitor based immunosuppression

PLoS One. 2012;7(7):e42011. doi: 10.1371/journal.pone.0042011. Epub 2012 Jul 25.

Abstract

Accumulating evidence suggests that Th17 cells play a role in the development of chronic allograft injury in transplantation of various organs. However, the influence of current immunosuppressants on Th17-associated immune responses has not been fully investigated. We prospectively investigated the changes in Th17 cells in peripheral blood mononuclear cells (PBMCs) collected before and 1 and 3 months after KT in 26 patients and we investigated the suppressive effect of tacrolimus on Th17 in vitro. In the early posttransplant period, the percentage of Th17 cells and the proportion of IL-17-producing cells in the effector memory T cells (TEM) were significantly increased at 3 months after transplantation compared with before transplantation (P<0.05), whereas Th1/Th2 cells and TEM cells were significantly decreased. The degree of increase in Th17 during the early posttransplant period was significantly associated with allograft function at 1 year after transplantation (r = 0.4, P<0.05). In vitro, tacrolimus suppressed Th1 and Th2 cells in a concentration-dependent manner, but did not suppress Th17 cells even at high concentration. This suggests that current immunosuppression based on tacrolimus is inadequate to suppress Th17 cells in KTRs, and dysregulation of Th17 may be associated with the progression of CAD.

Publication types

  • Clinical Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Biomarkers / metabolism
  • CD4-Positive T-Lymphocytes / drug effects
  • CD4-Positive T-Lymphocytes / immunology
  • Calcineurin Inhibitors*
  • Enzyme Inhibitors / pharmacology*
  • Female
  • Follow-Up Studies
  • Gene Expression Regulation / drug effects
  • Gene Expression Regulation / immunology
  • Humans
  • Immunosuppression Therapy / methods*
  • Kidney Transplantation / adverse effects
  • Male
  • Middle Aged
  • Postoperative Period
  • Tacrolimus / pharmacology
  • Th17 Cells / drug effects*
  • Th17 Cells / immunology*
  • Th17 Cells / metabolism
  • Time Factors
  • Transplantation, Homologous / adverse effects*

Substances

  • Biomarkers
  • Calcineurin Inhibitors
  • Enzyme Inhibitors
  • Tacrolimus

Grants and funding

This study was supported by a grant (A092258) from the Korea Healthcare Technology R&D Project, Ministry for Health, Welfare & Family Affairs, Republic of Korea. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.