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T-cell allorecognition of donor glutathione S-transferase T1 in plasma cell-rich rejection

AIM: To investigate the role of glutathione S-transferase T1 donor-specific T lymphocytes in plasma cell-rich rejection of liver allografts. METHODS: The study group included 22 liver transplant patients. Among them, 18 patients were mismatched for the glutathione S-transferase T1 (GSTT1) alleles (d...

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Autores principales: Martínez-Bravo, María José, Sánchez, Berta, Sousa, José Manuel, Acevedo, María José, Gómez-Bravo, Miguel Angel, Núñez-Roldán, Antonio, Aguilera, Isabel
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Baishideng Publishing Group Inc 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5620421/
https://www.ncbi.nlm.nih.gov/pubmed/29026463
http://dx.doi.org/10.4254/wjh.v9.i27.1115
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author Martínez-Bravo, María José
Sánchez, Berta
Sousa, José Manuel
Acevedo, María José
Gómez-Bravo, Miguel Angel
Núñez-Roldán, Antonio
Aguilera, Isabel
author_facet Martínez-Bravo, María José
Sánchez, Berta
Sousa, José Manuel
Acevedo, María José
Gómez-Bravo, Miguel Angel
Núñez-Roldán, Antonio
Aguilera, Isabel
author_sort Martínez-Bravo, María José
collection PubMed
description AIM: To investigate the role of glutathione S-transferase T1 donor-specific T lymphocytes in plasma cell-rich rejection of liver allografts. METHODS: The study group included 22 liver transplant patients. Among them, 18 patients were mismatched for the glutathione S-transferase T1 (GSTT1) alleles (don+/rec-), and 4 were matched (don+/rec+). Seven of the mismatched patients produced anti-GSTT1 antibodies and developed plasma cell-rich rejection (former de novo immune hepatitis). For the detection of specific T lymphocytes, peripheral blood mononuclear cells were collected and stored in liquid nitrogen. The memory T cell response was studied by adding to the cell cultures to a mix of 39 custom-made, 15-mer overlapping peptides, which covered the entire GSTT1 amino acid sequence. The specific cellular response to peptides was analyzed by flow cytometry using the markers CD8, CD4, IL-4 and IFNγ. RESULTS: Activation of CD8(+) T cells with different peptides was observed exclusively in the group of patients with plasma-cell rich rejection (3 out of 7), with production of IL-4 and/or IFNγ at a rate of 1%-4.92% depending on the peptides. The CD4(+) response was most common and not exclusive for patients with the disease, where 5 out of 7 showed percentages of activated cells from 1.24% to 31.34%. Additionally, two patients without the disease but with the mismatch had cells that became stimulated with some peptides (1.45%-5.18%). Highly unexpected was the finding of a double positive CD4(+)CD8(low) T cell population that showed the highest degree of activation with some of the peptides in 7 patients with the mismatch, in 4 patients with plasma cell-rich rejection and in 3 patients without the disease. Unfortunately, CD4(+)CD8(low) cells represent 1% of the total number of lymphocytes, and stimulation could not be analyzed in 9 patients due to the low number of gated cells. Cells from the 4 patients included as controls did not show activation with any of the peptides. CONCLUSION: Patients with GSTT1 mismatch can develop a specific T-cell response, but the potential role of this response in the pathogenesis of plasma cell-rich rejection is unknown.
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spelling pubmed-56204212017-10-12 T-cell allorecognition of donor glutathione S-transferase T1 in plasma cell-rich rejection Martínez-Bravo, María José Sánchez, Berta Sousa, José Manuel Acevedo, María José Gómez-Bravo, Miguel Angel Núñez-Roldán, Antonio Aguilera, Isabel World J Hepatol Retrospective Study AIM: To investigate the role of glutathione S-transferase T1 donor-specific T lymphocytes in plasma cell-rich rejection of liver allografts. METHODS: The study group included 22 liver transplant patients. Among them, 18 patients were mismatched for the glutathione S-transferase T1 (GSTT1) alleles (don+/rec-), and 4 were matched (don+/rec+). Seven of the mismatched patients produced anti-GSTT1 antibodies and developed plasma cell-rich rejection (former de novo immune hepatitis). For the detection of specific T lymphocytes, peripheral blood mononuclear cells were collected and stored in liquid nitrogen. The memory T cell response was studied by adding to the cell cultures to a mix of 39 custom-made, 15-mer overlapping peptides, which covered the entire GSTT1 amino acid sequence. The specific cellular response to peptides was analyzed by flow cytometry using the markers CD8, CD4, IL-4 and IFNγ. RESULTS: Activation of CD8(+) T cells with different peptides was observed exclusively in the group of patients with plasma-cell rich rejection (3 out of 7), with production of IL-4 and/or IFNγ at a rate of 1%-4.92% depending on the peptides. The CD4(+) response was most common and not exclusive for patients with the disease, where 5 out of 7 showed percentages of activated cells from 1.24% to 31.34%. Additionally, two patients without the disease but with the mismatch had cells that became stimulated with some peptides (1.45%-5.18%). Highly unexpected was the finding of a double positive CD4(+)CD8(low) T cell population that showed the highest degree of activation with some of the peptides in 7 patients with the mismatch, in 4 patients with plasma cell-rich rejection and in 3 patients without the disease. Unfortunately, CD4(+)CD8(low) cells represent 1% of the total number of lymphocytes, and stimulation could not be analyzed in 9 patients due to the low number of gated cells. Cells from the 4 patients included as controls did not show activation with any of the peptides. CONCLUSION: Patients with GSTT1 mismatch can develop a specific T-cell response, but the potential role of this response in the pathogenesis of plasma cell-rich rejection is unknown. Baishideng Publishing Group Inc 2017-09-28 2017-09-28 /pmc/articles/PMC5620421/ /pubmed/29026463 http://dx.doi.org/10.4254/wjh.v9.i27.1115 Text en ©The Author(s) 2017. Published by Baishideng Publishing Group Inc. All rights reserved. http://creativecommons.org/licenses/by-nc/4.0/ 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.
spellingShingle Retrospective Study
Martínez-Bravo, María José
Sánchez, Berta
Sousa, José Manuel
Acevedo, María José
Gómez-Bravo, Miguel Angel
Núñez-Roldán, Antonio
Aguilera, Isabel
T-cell allorecognition of donor glutathione S-transferase T1 in plasma cell-rich rejection
title T-cell allorecognition of donor glutathione S-transferase T1 in plasma cell-rich rejection
title_full T-cell allorecognition of donor glutathione S-transferase T1 in plasma cell-rich rejection
title_fullStr T-cell allorecognition of donor glutathione S-transferase T1 in plasma cell-rich rejection
title_full_unstemmed T-cell allorecognition of donor glutathione S-transferase T1 in plasma cell-rich rejection
title_short T-cell allorecognition of donor glutathione S-transferase T1 in plasma cell-rich rejection
title_sort t-cell allorecognition of donor glutathione s-transferase t1 in plasma cell-rich rejection
topic Retrospective Study
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5620421/
https://www.ncbi.nlm.nih.gov/pubmed/29026463
http://dx.doi.org/10.4254/wjh.v9.i27.1115
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