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Background Renal resistive index (RI) predicts mortality in renal transplant recipients, but we do not know whether this is true in diabetic patients. The objective of this study was to analyse the long-term predictive value of RI for death with a functioning graft (DWFG) in renal transplant recipients with or without pre-transplant diabetes. Methods We conducted a retrospective study in 1800 renal transplant recipients between 1985 and 2017 who were followed for up to 30 years (total observation period: 14 202 patient years). Donor and recipient characteristics at time of transplantation and at 3 months were reviewed. The long-term predictive value of RI for DWFG and the age–RI and arterial pressure–RI relationships were assessed. Results A total of 284/1800 (15.7%) patients had diabetes mellitus before transplantation. RI was <0.75 in 1327/1800 patients (73.7%). High RI was associated with a higher risk of DWFG in non-diabetic patients [hazard ratio (HR) = 3.39, 95% confidence interval 2.50–4.61; P < 0.001], but not in patients with pre-transplant diabetes (HR = 1.25, 0.70–2.19; P = 0.39), even after multiple adjustments. There was no interaction between diabetes and age. In contrast, there was an interaction between RI and pulse pressure. Conclusion Our study indicates that RI is not a predictor of DWFG in diabetic renal transplant recipients, in contrast to non-diabetic recipients. These findings could be due to a different age–RI or pulse pressure–RI relationship. [ABSTRACT FROM AUTHOR]

Human iTreg cells regulate CD8+ T cell cytotoxicityRegulatory T cells (Treg) play a crucial role in controlling immunity and transplant rejection. Two main groups of Treg have been described: antigen-induced Treg (iTreg) and natural Treg (nTreg). The ways to induce and the mechanisms of action of Treg subsets remained ill defined, particularly for their effects on CD8+ T cells. CD8+ T cells are major agents in the rejection of allografts; the aim of this study is to investigate the effects exerted on CD8+ T cells by human CD4+ iTreg induced by mycophenolic acid-treated dendritic cells. iTreg suppress the proliferation of CD8+ T cells by allogeneic cell–cell interaction with mature dendritic cells and irrespectively of the TCR specificity of the CD8+ T cells and cell–cell contact of iTreg with CD8+ T cells. In our model, this suppression is independent of the action of IL-10 and TGF-β1. iTreg were able to modify phenotype and inhibited IFN-γ and TNF-α secretion by CD8+ T cells. Most interestingly, iTreg inhibit the synthesis of perforin and of granzymes A and B by CD8+ T cells and impaired their cytotoxicity against allogeneic targets. In summary, our study showed the involvement of iTreg in the down-regulation of cytotoxic responses mediated by CD8+ T cells in an allospecific context. Following studies that have shown the existence of a regulation control exerted by iTreg on CD4+ T cells and dendritic cells, this work ultimately shows that this regulation can reach CD8+ T-cell functions. [ABSTRACT FROM PUBLISHER]

A large body of evidence has been accumulated from experimental models in the past decade to support the critical role of Foxp3-expressing regulatory T cells (Tregs) in the suppression of alloimmune responses. This has prompted transplant clinicians to investigate whether Foxp3 analysis might be used as an immunodiagnostic tool for better assessment of the significance of graft infiltrate and to predict its impact on graft outcome. However, conflicting results have emerged from these studies and may have generated more confusion than clarification. Foxp3 expression has been antagonistically correlated with either good or poor prognosis. We discuss here how methodological issues and specific clinical settings may have accounted for the discrepancies between the results of these studies. Depending on many factors, including the techniques used, the method of sampling normalization, the extent of intra-graft inflammation, the immunosuppressive regimen and the depletion or repletion of T lymphocyte compartment, the significance of Foxp3 expression may vary. We propose here the conditions to be fulfilled in order to use Foxp3 analysis as a relevant biomarker for graft outcome assessment. Far from challenging the key role of Tregs in dampening alloimmune responses, this review highlights the need for technical harmonization and standards. [ABSTRACT FROM AUTHOR]