Objective To investigate the role of OX40 in the mechanisms of memory T cells in islet transplant tolerance. Methods The expression of OX40 on native, like memory and memory CD8 + T cells was detected by RT - PCR. Spl...Objective To investigate the role of OX40 in the mechanisms of memory T cells in islet transplant tolerance. Methods The expression of OX40 on native, like memory and memory CD8 + T cells was detected by RT - PCR. Splenic T ceels from B6 mice were injected into Rag - / - mice via the tail vein,and the Rag mice were divided into three groups ( n = 8 each) :展开更多
Objective： To investigate the expression of OX40 ligand（OX40L） on C-reactive protein（CRP）-triggered mouse aorta endothelial cells （MAECs） in vitro. Methods： MAECs from aorta were isolated by digestion with col...Objective： To investigate the expression of OX40 ligand（OX40L） on C-reactive protein（CRP）-triggered mouse aorta endothelial cells （MAECs） in vitro. Methods： MAECs from aorta were isolated by digestion with collagenase type II. The cell growth was confirmed by morphological characteristics and the immunological marker, factor Ⅷ（or Willebrand factor, vWF）. The expression of OX40L by MAECs was detected by RT-PCR and western blot after incubating with 100μg/ml CRP for 48 hours. Results： Twenty-day cultures of MAECs formed confluent monolayer of a cobblestone pattern. RT-PCR and western blot assay showed that the level of OX40L expression in MAECs receiving CRP treatment was higher than control. Conclusion： A reliable method is described to isolate and propagate MAECs. CRP upregulates OX40L expression in MAECs.展开更多
Objective: To study the correlation of peripheral blood COS, OX40 and CD40 expression with disease activity in patients with lupus nephritis (LN). Methods: Patients who were diagnosed with stable and active lupus neph...Objective: To study the correlation of peripheral blood COS, OX40 and CD40 expression with disease activity in patients with lupus nephritis (LN). Methods: Patients who were diagnosed with stable and active lupus nephritis in Zigong First People's Hospital between May 2014 and March 2017 were selected and enrolled in stable LN group and active LN group respectively;healthy volunteers who received physical examination during the same period were chosen as control group. The ICOS, OX40 and CD40 mRNA expression in peripheral blood nuclear cells as well as the levels of cytokines and disease activity-related indexes in serum were measured. Results: ICOS, OX40 and CD40 mRNA expression in peripheral blood mononuclear cells as well as IL-4, IL-5, IL-10, anti-C1q antibody and anti-ds-DNA antibody levels in serum of stable LN group and active LN group were significantly higher than those of control group while TNF-α, IFN-γ, C3 and C4 levels in serum were significantly lower than those of control group;the changes in active LN group were more significant than those in stable LN group;ICOS, OX40 and CD40 mRNA expression in peripheral blood mononuclear cells of patients with LN were positively correlated with IL-4, IL-5, IL-10, anti-C1q antibody and anti-ds-DNA antibody levels in serum, and negatively correlated with TNF-α, IFN-γ, C3 and C4 levels in serum. Conclusion: High expression of ICOS, OX40 and CD40 in the peripheral blood of patients with LN are closely related to the Th1/Th2 shifting and the disease activity.展开更多
The low objective response rates and severe side effects largely limit the clinical outcomes of immune checkpoint blockade(ICB)therapy.Here,a tumor“self-killing”therapy based on gene-guided OX40L anchoring to tumor ...The low objective response rates and severe side effects largely limit the clinical outcomes of immune checkpoint blockade(ICB)therapy.Here,a tumor“self-killing”therapy based on gene-guided OX40L anchoring to tumor cell membrane was reported to boost ICB therapy.We developed a highly efficient delivery system HA/PEI-KT(HKT)to co-deliver the OX40L plasmids and unmethylated CG-enriched oligodeoxynucleotide(CpG).On the one hand,CpG induced the expression of OX40 on T cells within tumors.On the other hand,OX40L plasmids achieved the OX40L anchoring on the tumor cell membrane to next promote T cells responses via OX40/OX40L axis.Such synergistic tumor“self-killing”strategy finally turned“cold”tumors to“hot”,to sensitize tumors to programmed cell death protein 1/programmed cell death ligand 1(PD-1/PD-L1)blockade therapy,and promoted an immune-mediated tumor regression in both B16F10 and 4T1 tumor models,with prevention of tumor recurrence and metastasis.To avoid the side effects,the gene-guided OX40L anchoring and PD-L1 silencing was proposed to replace the existing antibody therapy,which showed negligible toxicity in vivo.Our work provided a new possibility for tumor“self-killing”immunotherapy to treated various solid tumors.展开更多
文摘Objective To investigate the role of OX40 in the mechanisms of memory T cells in islet transplant tolerance. Methods The expression of OX40 on native, like memory and memory CD8 + T cells was detected by RT - PCR. Splenic T ceels from B6 mice were injected into Rag - / - mice via the tail vein,and the Rag mice were divided into three groups ( n = 8 each) :
基金supported by National Natural Science Founda-tion of China(30770894)Medical Foundation key scholar of Jiangsu Province(RC2007037)
文摘Objective： To investigate the expression of OX40 ligand（OX40L） on C-reactive protein（CRP）-triggered mouse aorta endothelial cells （MAECs） in vitro. Methods： MAECs from aorta were isolated by digestion with collagenase type II. The cell growth was confirmed by morphological characteristics and the immunological marker, factor Ⅷ（or Willebrand factor, vWF）. The expression of OX40L by MAECs was detected by RT-PCR and western blot after incubating with 100μg/ml CRP for 48 hours. Results： Twenty-day cultures of MAECs formed confluent monolayer of a cobblestone pattern. RT-PCR and western blot assay showed that the level of OX40L expression in MAECs receiving CRP treatment was higher than control. Conclusion： A reliable method is described to isolate and propagate MAECs. CRP upregulates OX40L expression in MAECs.
文摘Objective: To study the correlation of peripheral blood COS, OX40 and CD40 expression with disease activity in patients with lupus nephritis (LN). Methods: Patients who were diagnosed with stable and active lupus nephritis in Zigong First People's Hospital between May 2014 and March 2017 were selected and enrolled in stable LN group and active LN group respectively;healthy volunteers who received physical examination during the same period were chosen as control group. The ICOS, OX40 and CD40 mRNA expression in peripheral blood nuclear cells as well as the levels of cytokines and disease activity-related indexes in serum were measured. Results: ICOS, OX40 and CD40 mRNA expression in peripheral blood mononuclear cells as well as IL-4, IL-5, IL-10, anti-C1q antibody and anti-ds-DNA antibody levels in serum of stable LN group and active LN group were significantly higher than those of control group while TNF-α, IFN-γ, C3 and C4 levels in serum were significantly lower than those of control group;the changes in active LN group were more significant than those in stable LN group;ICOS, OX40 and CD40 mRNA expression in peripheral blood mononuclear cells of patients with LN were positively correlated with IL-4, IL-5, IL-10, anti-C1q antibody and anti-ds-DNA antibody levels in serum, and negatively correlated with TNF-α, IFN-γ, C3 and C4 levels in serum. Conclusion: High expression of ICOS, OX40 and CD40 in the peripheral blood of patients with LN are closely related to the Th1/Th2 shifting and the disease activity.
基金This work was financially supported by the National Key R&D Program of China(2021YFB3800900)National Natural Science Foundation of China(51925305,51873208,51833010,51803210,51973217)Jilin province science and technology development program(20200201075JC).
文摘The low objective response rates and severe side effects largely limit the clinical outcomes of immune checkpoint blockade(ICB)therapy.Here,a tumor“self-killing”therapy based on gene-guided OX40L anchoring to tumor cell membrane was reported to boost ICB therapy.We developed a highly efficient delivery system HA/PEI-KT(HKT)to co-deliver the OX40L plasmids and unmethylated CG-enriched oligodeoxynucleotide(CpG).On the one hand,CpG induced the expression of OX40 on T cells within tumors.On the other hand,OX40L plasmids achieved the OX40L anchoring on the tumor cell membrane to next promote T cells responses via OX40/OX40L axis.Such synergistic tumor“self-killing”strategy finally turned“cold”tumors to“hot”,to sensitize tumors to programmed cell death protein 1/programmed cell death ligand 1(PD-1/PD-L1)blockade therapy,and promoted an immune-mediated tumor regression in both B16F10 and 4T1 tumor models,with prevention of tumor recurrence and metastasis.To avoid the side effects,the gene-guided OX40L anchoring and PD-L1 silencing was proposed to replace the existing antibody therapy,which showed negligible toxicity in vivo.Our work provided a new possibility for tumor“self-killing”immunotherapy to treated various solid tumors.
