Exp Mol Med.  2011 Nov;43(11):630-637. 10.3858/emm.2011.43.11.071.

Higher infiltration by Th17 cells compared with regulatory T cells is associated with severe acute T-cell-mediated graft rejection

• Chung BH
• Oh HJ
• Piao SG
• Sun IO
• Kang SH
• Choi SR
• Park HS
• Choi BS
• Choi YJ
• Park CW
• Kim YS
• Cho ML
• Yang CW

• KMID: 1025166
• DOI: http://doi.org/10.3858/emm.2011.43.11.071

Abstract

The aim of this study was to evaluate whether the Th17 and Treg cell infiltration into allograft tissue is associated with the severity of allograft dysfunction and tissue injury in acute T cell-mediated rejection (ATCMR). Seventy-one allograft tissues with biopsy-proven ATCMR were included. The biopsy specimens were immunostained for FOXP3 and IL-17. The allograft function was assessed at biopsy by measuring serum creatinine (Scr) concentration, and by applying the modified diet in renal disease (MDRD) formula, which provides the estimated glomerular filtration rate (eGFR). The severity of allograft tissue injury was assessed by calculating tissue injury scores using the Banff classification. The average numbers of infiltrating Treg and Th17 cells were 11.6 +/- 12.2 cells/mm2 and 5.6 +/- 8.0 cells/mm2, respectively. The average Treg/Th17 ratio was 5.6 +/- 8.2. The Treg/Th17 ratio was significantly associated with allograft function (Scr and MDRD eGFR) and with the severity of interstitial injury and tubular injury (P < 0.05, all parameters). In separate analyses of the number of infiltrating Treg and Th17 cells, Th17 cell infiltration was significantly associated with allograft function and the severity of tissue injury. By contrast, Treg cell infiltration was not significantly associated with allograft dysfunction or the severity of tissue injury. The results of this study show that higher infiltration of Th17 cell compared with Treg cell is significantly associated with the severity of allograft dysfunction and tissue injury.

Keyword

FOXP3 protein, human; graft rejection; interleukin-17; Th17 cells; T-lymphocytes, regulatory; transplantation, homologous

MeSH Terms

Acute Disease
Creatinine/metabolism
Forkhead Transcription Factors/metabolism
Graft Rejection/*etiology/pathology
Humans
Immunoenzyme Techniques
Interleukin-17/*metabolism
Kidney Transplantation/*adverse effects
Retrospective Studies
T-Lymphocytes, Regulatory/*immunology/pathology
Th17 Cells/*immunology/pathology
Transplantation, Homologous