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

Byung Ha Chung,Hoon Suk Park,Yeong Jin Choi,Yong-Soo Kim,Seok Hui Kang,Mi-La Cho,In O Sun,Shang Guo Piao,Hye Jwa Oh,Cheol Whee Park,Bum Soon Choi,Chul Woo Yang,Sun Ryoung Choi

doi:10.3858/emm.2011.43.11.071

Byung Ha Chung, Hoon Suk Park + Show 11 more

Open Access

https://doi.org/10.3858/emm.2011.43.11.071

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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.

Highlights

FOXP3+ regulatory T (Treg) cells play an important role in suppressing immune responses in various immune disorders (Hori et al, 2003; Allan et al, 2005) and are expected to have beneficial effects by suppressing alloimmune responses in kidney transplantation
We investigated the infiltration by FOXP3 positive regulatory T cell (Treg) and Th17 cells, and the Treg/Th17 ratio in renal transplant biopsies for cause, focusing on their association with the severity of allograft rejection
Our results demonstrate clearly that the Treg/Th17 ratio and Th17 cell infiltration were closely associated with the severity of allograft dysfunction and tissue injury in acute T cell-mediated rejection (ATCMR)

Summary

Introduction

FOXP3+ regulatory T (Treg) cells play an important role in suppressing immune responses in various immune disorders (Hori et al, 2003; Allan et al, 2005) and are expected to have beneficial effects by suppressing alloimmune responses in kidney transplantation. A high number of FOXP3+ Treg cells was associated with preserved allograft function or less severe interstitial inflammation (Taflin et al, 2010). The association between Treg cell infiltration and the severity of allograft tissue injury in acute T cell-mediated rejection (ATCMR) is controversial. Treg/Th17 ratio and allograft tissue injury 631 et al, 2009). Th17 cells can interconvert with Treg cells depending on the microenvironment (Lee et al, 2009). The imbalance between Th17 and Treg cells has been proposed as an important mechanism that modulates immune responses in various autoimmune disorders (Lee et al, 2009; Nistala and Wedderburn, 2009; Ochs et al, 2009; Eastaff-Leung et al, 2010; Shin et al, 2010)

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