Clinical significance of the ratio between FOXP3 positive regulatory T cell and interleukin‐17 secreting cell in renal allograft biopsies with acute T‐cell‐mediated rejection

Abstract

SummaryThe aim of this study is to investigate the clinical significance of the ratio between interleukin-17 (IL-17) secreting cell and FOXP3-positive regulatory T cell (FOXP3 + Treg) infiltration in renal allograft tissues with acute T-cell-mediated rejection (ATCMR). Fifty-six patients with biopsy-proven ATCMR were included. Infiltration of FOXP3 + Treg and IL-17-secreting cells was evaluated with immunostaining for FOXP3 or IL-17 on the biopsy specimens, and the patients were divided into the FOXP3 high group (Log FOXP3/IL-17 > 0Á45) or the IL-17 high group (Log FOXP3/ IL-17 < 0Á45). We compared the allograft function, severity of tissue injury, and clinical outcome between the two groups. In the IL-17 high group, allograft function was significantly decreased compared with the FOXP3 high group (P < 0Á05). The severity of interstitial and tubular injury in the IL-17 high group was higher than the FOXP3 high group (P < 0Á05). The proportions of steroid-resistant rejection, incomplete recovery and recurrent ATCMR were higher in the IL-17 high group than in the FOXP3 high group (all indicators, P < 0Á05). The IL-17 high group showed lower 1-year (54% versus 90%, P < 0Á05) and 5-year (38% versus 85%, P < 0Á05) allograft survival rates compared with the FOXP3 high group. Multivariate analysis revealed that the FOXP3/IL-17 ratio was a significant predictor for allograft outcome. The FOXP3/IL-17 ratio is a useful indicator for representing the severity of tissue injury, allograft dysfunction and for predicting the clinical outcome of ATCMR.

Mycophenolic acid derivative 118 improves outcome of skin grafts by suppressing IL-17 production

“…Initially, the Th1 response was thought to play the pivotal pathogenic role [21] . However, this notion was challenged by the findings that IL-17 was critically associated with allograft rejection [22,23] . IL-17 is an important mediator that affects downstream inflammatory events, predominantly by recruiting neutrophils and monocytes to the grafts through the upregulation of monocyte and neutrophil-recruiting chemokines [24,25] .…”

The number of FoxP3+ cells in transbronchial lung allograft biopsies does not predict bronchiolitis obliterans syndrome within the first five years after transplantation

“…In addition, regulatory T cells do show significant plasticity and can lose their regulatory function. The final outcome is believed to depend on the balance between regulatory and effector cells , which is not assessed in this study.…”

Interpretation of transplant biopsies and immune responses following Treg cell therapy

“…Another consideration is that, even in instances of spontaneous(9) or induced transplant tolerance(10), lymphocytes (including Treg) can be found within allografts. Foxp3 positive T cells have also been demonstrated in numerous human allograft biopsy studies(11, 12). …”