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Reduced TCR-signalling contributes to impaired Th17 responses in tolerant kidney transplant recipients
- Source :
- Nova-Lamperti, E, Romano, M, Christakoudi, S, Runglall, M, McGregor, R, Mobillo, P, Kamra, Y, Tsui, T-L, Norris, S, John, S, Boardman, D A, Lechler, R I, Lombardi, G, Hernandez-Fuentes, M P 2017, ' Reduced TCR-signalling contributes to impaired Th17 responses in tolerant kidney transplant recipients ', Transplantation . https://doi.org/10.1097/TP.0000000000001920, e17, e10
- Publication Year :
- 2017
-
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.
- Subjects :
- Adult
CD4-Positive T-Lymphocytes
Male
0301 basic medicine
Tcr signaling
Receptors, Antigen, T-Cell
030230 surgery
www.GAMBITstudy.co.uk
Kidney transplant
Article
03 medical and health sciences
0302 clinical medicine
Immune system
Antigen
medicine
Journal Article
Animals
Humans
Cell Lineage
Extracellular Signal-Regulated MAP Kinases
Receptor
Interleukin 6
Kidney transplantation
Aged
Transplantation
biology
Interleukin-6
business.industry
11 Medical And Health Sciences
Middle Aged
medicine.disease
Kidney Transplantation
030104 developmental biology
Immunology
biology.protein
Th17 Cells
Surgery
Female
Transplantation Tolerance
Signal transduction
business
Chickens
Signal Transduction
Subjects
Details
- Language :
- English
- Database :
- OpenAIRE
- Journal :
- Nova-Lamperti, E, Romano, M, Christakoudi, S, Runglall, M, McGregor, R, Mobillo, P, Kamra, Y, Tsui, T-L, Norris, S, John, S, Boardman, D A, Lechler, R I, Lombardi, G, Hernandez-Fuentes, M P 2017, ' Reduced TCR-signalling contributes to impaired Th17 responses in tolerant kidney transplant recipients ', Transplantation . https://doi.org/10.1097/TP.0000000000001920, e17, e10
- Accession number :
- edsair.doi.dedup.....d54b50580cab67aeb97c30cdef4aae19