T-cell allorecognition of donor glutathione S-transferase T1 in plasma cell-rich rejection
Autor: | Antonio Núñez-Roldán, Maria J. Acevedo, B. Sanchez, Isabel Aguilera, J.M. Sousa, María José Martínez-Bravo, Miguel Ángel Gómez-Bravo |
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Rok vydání: | 2017 |
Předmět: |
Donor-specific glutathione S-transferase T1 antibodies
Donor/recipient mismatch T cell De novo immune hepatitis Population Indirect presentation 030230 surgery Plasma cell Peripheral blood mononuclear cell Flow cytometry 03 medical and health sciences 0302 clinical medicine Retrospective Study Medicine education education.field_of_study Hepatology biology medicine.diagnostic_test business.industry Molecular biology Glutathione S-transferase T1-memory T cells medicine.anatomical_structure biology.protein 030211 gastroenterology & hepatology Antibody business Memory T cell CD8 |
Zdroj: | World Journal of Hepatology |
ISSN: | 1948-5182 |
Popis: | 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. |
Databáze: | OpenAIRE |
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