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©The Author(s) 2018. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Transplant. Feb 24, 2018; 8(1): 23-37
Published online Feb 24, 2018. doi: 10.5500/wjt.v8.i1.23
In vitro intracellular IFNγ, IL-17 and IL-10 producing T cells correlates with the occurrence of post-transplant opportunistic infection in liver and kidney recipients
Francisco Boix, Santiago Llorente, Jorge Eguía, Gema Gonzalez-Martinez, Rafael Alfaro, Jose A Galián, Jose A Campillo, María Rosa Moya-Quiles, Alfredo Minguela, Jose A Pons, Manuel Muro
Francisco Boix, Jorge Eguía, Gema Gonzalez-Martinez, Rafael Alfaro, Jose A Galián, Jose A Campillo, María Rosa Moya-Quiles, Alfredo Minguela, Manuel Muro, Department of Immunology, Clinical University Hospital Virgen de la Arrixaca-IMIB, Clinical University Hospital ‘Virgen Arrixaca’, Murcia 30120, Spain
Santiago Llorente, Department of Nephrology, Clinical University Hospital ‘Virgen de la Arrixaca-IMIB’, Clinical University Hospital ‘Virgen Arrixaca’, Murcia 30120, Spain
Jose A Pons, Digestive Medicine Service, Clinical University Hospital ‘Virgen de la Arrixaca-IMIB’, Clinical University Hospital ‘Virgen Arrixaca’, Murcia 30120, Spain
Author contributions: Muro M planned the experiments, overviewed the research project and reviewed the manuscript; Eguía J, Gonzalez-Martinez G, Alfaro R and Galián JA performed the experimental worked supervised by Boix F; Boix F, Campillo JA and Moya-Quiles MR analysed the data; Minguela A reviewed the manuscript; Llorente S and Pons JA provided clinical data and reviewed the manuscript; Boix F and Muro M equally participated in the writing of the manuscript.
Supported by Instituto de Salud Carlos III, Spanish Ministry of Economy and Competitiveness, No. PI15/01370; Co-funding of the European Union with European Fund of Regional Development (FEDER) with the principle of “A manner to build Europe”.
Institutional review board statement: The study protocol, standard operating procedures and good manufacturing practice protocols used in this research were approved by the institutional ethical committee.
Informed consent statement: Formal informed consent was obtained from both patients and healthy controls.
Conflict-of-interest statement: Authors have no relevant conflicts of interest to disclose.
Data sharing statement: No additional data are available.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Correspondence to: Francisco Boix, PhD, Doctor, Senior Scientist, Department of Immunology, Clinical University Hospital ́‘Virgen de la Arrixaca-IMIB’, Clinical University Hospital ‘Virgen Arrixaca’, Murcia 30120, Spain.
francisco.boix-giner@nhsbt.nhs.uk
Telephone: +34-968-369599 Fax: +34-968-369678
Received: November 6, 2017
Peer-review started: November 7, 2017
First decision: November 20, 2017
Revised: January 13, 2018
Accepted: February 4, 2018
Article in press: February 5, 2018
Published online: February 24, 2018
Processing time: 109 Days and 22 Hours
ARTICLE HIGHLIGHTS
Research background
Nowadays liver and kidney transplant are well-established therapeutic options for patients with end stage liver and kidney diseases. However, the administration of immunosuppressant is not exempt of side effects that ultimately could lead to worse transplant outcome.
Research motivation
Monitoring of adaptive immune response by flow cytometry provides means of further understanding on how T lymphocytes vary throughout the post-transplant period.
Research objectives
In this study, the authors aim to validate the intracellular cytokine production functional assay as means of cell-mediated immunity monitoring of post-transplant patients with opportunistic infection.
Research methods
A longitudinal study was carried out in two cohorts of transplant recipients where patients were prospectively monitored for one year post-transplantation.
Research results
LTr with OI had significantly lower % of CD8+CD69+IFNγ+ T cells at 60, 90 and 180 d post-transplantation. Higher % of CD4+CD69+IL-10+ as well as CD4+CD69+IL-17+ T cells were yet reported at 30, 60 and 90 d. KTr with OI had significantly lower % of CD4+CD69+IFNγ+ T cells at 30, 60, 90 and 180 d post-transplantation whereas IL-10-producing CD4+ and CD8+ T cells were significantly higher at 30, 90 and 180 d.
Research conclusions
The quantification of intracellular cytokine production by flow cytometry has been validated as a reliable functional assay that provides trustworthy information to a better management of transplanted patients. The occurrence of opportunistic infection was significantly correlated with an imbalance between TH1, TH2 and TH17 cells in both liver and kidney transplant recipients.
Research perspectives
Post-transplant administration of immunosuppressant as well as prophylaxis therapies could be adapted according to the levels of TH1, TH2 TH17 in an individual basis.