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Reduced TCR-signalling contributes to impaired Th17 responses in tolerant kidney transplant recipients.

Reduced TCR-signalling contributes to impaired Th17 responses in tolerant kidney transplant recipients.
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Nova-Lamperti E, Romano M, Christakoudi S, Runglall M, McGregor R, Mobillo P, Kamra Y, Tsui TL, Norris S, John S, Boardman DA, Lechler RI, Lombardi G, Hernandez-Fuentes MP, ,


Nova-Lamperti E, Romano M, Christakoudi S, Runglall M, McGregor R, Mobillo P, Kamra Y, Tsui TL, Norris S, John S, Boardman DA, Lechler RI, Lombardi G, Hernandez-Fuentes MP, , (click to view)

Nova-Lamperti E, Romano M, Christakoudi S, Runglall M, McGregor R, Mobillo P, Kamra Y, Tsui TL, Norris S, John S, Boardman DA, Lechler RI, Lombardi G, Hernandez-Fuentes MP, ,

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Transplantation 2017 09 12() doi 10.1097/TP.0000000000001920
Abstract
BACKGROUND
The development of spontaneous kidney transplant tolerance has been associated with numerous B cell-related immune alterations. We have previously shown that tolerant recipients exhibit reduced B cell receptor (BCR) signalling and higher IL-10 production than healthy volunteers. However, it is unclear whether CD4T cells from tolerant recipients also display an antiinflammatory profile that could contribute to graft maintenance.

METHODS
CD4T cells were isolated from kidney transplant recipients who were identified as being tolerant recipients, patients with chronic-rejection or healthy volunteers. CD4T cells from the 3 groups were compared in terms of their gene expression profile, phenotype and functionally upon activation.

RESULTS
Gene expression analysis of transcription factors and signalling proteins, in addition to surface proteins expression and cytokine production, revealed that tolerant recipients possessed fewer Th17 cells and exhibited reduced Th17 responses, relative to patients with chronic rejection or healthy volunteers. Furthermore, impaired TCR signalling and altered cytokine cooperation by monocytes contributed to the development of Th17 cells in tolerant recipients.

CONCLUSIONS
These data suggest that defective proinflammatory Th17 responses may contribute to the prolonged graft survival and stable graft function, which is observed in tolerant recipients in the absence of immunosuppressive agents.This is an open-access article distributed under the terms of the Creative Commons Attribution-Non Commercial License 4.0 (CCBY-NC), where it is permissible to download, share, remix, transform, and buildup the work provided it is properly cited. The work cannot be used commercially without permission from the journal.

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