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 pa...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 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 IFNγat 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.展开更多
基金Supported by The Spanish Ministry of Economy,Instituto de Salud Carlos III,Nos.10/2332 and 11/857the Andalusian government,No.PI-0332-2007,for which Martinez-Bravo MJ was a pre-doctoral fellow
文摘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 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 IFNγat 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.
