Objective To investigate the possible influence of immunosuppressive therapy,including sirolimus ( SRL) and calcineurin inhibitors ( CNI,tacrolimus) ,on level of Treg in liver allo - graft recipients. Methods Forty - ...Objective To investigate the possible influence of immunosuppressive therapy,including sirolimus ( SRL) and calcineurin inhibitors ( CNI,tacrolimus) ,on level of Treg in liver allo - graft recipients. Methods Forty - seven liver transplant recipients with stable liver function were assessed for at least 2 years,and divided into展开更多
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 ...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 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 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
Achieving net-zero CO_(2)emissions is the current main focus of China’s carbon neutrality goal.However,non-CO_(2)greenhouse gases(GHGs)are more powerful climate forcers,making their emission reduction an opportunity ...Achieving net-zero CO_(2)emissions is the current main focus of China’s carbon neutrality goal.However,non-CO_(2)greenhouse gases(GHGs)are more powerful climate forcers,making their emission reduction an opportunity to rapidly mitigate future warming.Here,we evaluate non-CO_(2)mitigation potentials,costs and climate benefits in the context of China’s carbon neutrality goals.The assessment is conducted by coupling the integrated assessment model GCAM with a climate emulator.The findings indicate that mitigation technologies can largely reduce fluorinated gas emissions from industrial sectors,but long-term non-CO_(2)reductions of energy sector activities rely heavily on fuel switching.Furthermore,the cumulative costs of deploying non-CO_(2)mitigation technologies are projected to be less than 10%of the total costs of achieving carbon neutrality from 2020 to 2060.If non-CO_(2)mitigation measures are included in the overall mitigation portfolio,the benefits of avoided warming would by far outweigh the total mitigation cost increase.Our results thus highlight that incorporating a wider suite of GHGs into climate change mitigation strategies can enhance the cost-effectiveness of mitigation efforts.展开更多
文摘Objective To investigate the possible influence of immunosuppressive therapy,including sirolimus ( SRL) and calcineurin inhibitors ( CNI,tacrolimus) ,on level of Treg in liver allo - graft recipients. Methods Forty - seven liver transplant recipients with stable liver function were assessed for at least 2 years,and divided into
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 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 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.
基金supported by the National Key Research and Development Program of China(2022YFC3105304)the National Natural Science Foundation of China(72303136)+1 种基金the Shandong Natural Science Foundation of China(ZR2023QG002)Major grant in National Social Sciences of China(23VRC037,24VHQ018).
文摘Achieving net-zero CO_(2)emissions is the current main focus of China’s carbon neutrality goal.However,non-CO_(2)greenhouse gases(GHGs)are more powerful climate forcers,making their emission reduction an opportunity to rapidly mitigate future warming.Here,we evaluate non-CO_(2)mitigation potentials,costs and climate benefits in the context of China’s carbon neutrality goals.The assessment is conducted by coupling the integrated assessment model GCAM with a climate emulator.The findings indicate that mitigation technologies can largely reduce fluorinated gas emissions from industrial sectors,but long-term non-CO_(2)reductions of energy sector activities rely heavily on fuel switching.Furthermore,the cumulative costs of deploying non-CO_(2)mitigation technologies are projected to be less than 10%of the total costs of achieving carbon neutrality from 2020 to 2060.If non-CO_(2)mitigation measures are included in the overall mitigation portfolio,the benefits of avoided warming would by far outweigh the total mitigation cost increase.Our results thus highlight that incorporating a wider suite of GHGs into climate change mitigation strategies can enhance the cost-effectiveness of mitigation efforts.
