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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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