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

Martínez-Bravo, MJ; Sánchez, B; Sousa, JM; Acevedo, MJ; Gómez-Bravo, MA; Núñez-Roldán, A; Aguilera, I; (2017) T-cell allorecognition of donor glutathione S-transferase T1 in plasma cell-rich rejection. World Journal of Hepatology , 9 (27) pp. 1115-1124. 10.4254/wjh.v9.i27.1115. Green open access

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Abstract

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+CD8low 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+CD8low 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.

Type: Article
Title: T-cell allorecognition of donor glutathione S-transferase T1 in plasma cell-rich rejection
Location: United States
Open access status: An open access version is available from UCL Discovery
DOI: 10.4254/wjh.v9.i27.1115
Publisher version: http://doi.org/10.4254/wjh.v9.i27.1115
Language: English
Additional information: Copyright ©The Author(s) 2017. 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/
Keywords: De novo immune hepatitis, Donor-specific glutathione S-transferase T1 antibodies, Donor/recipient mismatch, Glutathione S-transferase T1-memory T cells, Indirect presentation
UCL classification: UCL > Provost and Vice Provost Offices
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > UCL School of Pharmacy
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > UCL School of Pharmacy > SoP Pharmaceutical and Bio Chemistry
URI: https://discovery.ucl.ac.uk/id/eprint/10041660
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