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

World Journal of Hepatology 2017年第27期9卷 1115-1124页

作者： María José Martínez-Bravo Berta Sánchez José Manuel Sousa María José Acevedo Miguel Angel Gómez-Bravo Antonio Núnez-Roldán Isabel Aguilera Immunology Service Instituto de Biomedicina de Sevilla Hospital Universitario Virgen del Rocío/CSIC/Universidad de Sevilla Digestive Diseases Service Hospital Universitario Virgen del Rocío Liver Transplant Unit Hospital Universitario Virgen del Rocío

AIM To investigate the role of glutathione S-transferase T1 donor-specific T lymphocytes in plasma cell-rich rejection of liver *** 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 Tlymphocytes, 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

关键词： Donor-specific glutathione S-transferase T1 antibodies Indirect presentation Glutathione S-transferase T1-memory T cells de novo immune hepatitis Donor/recipient mismatch

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