Background:Immune checkpoint ligand-receptor interactions appear to be associated with multiple myeloma(MM)progression.Simultaneously,previous studies showed the possibility of PD-1 and TIM-3 expression on T cells upo...Background:Immune checkpoint ligand-receptor interactions appear to be associated with multiple myeloma(MM)progression.Simultaneously,previous studies showed the possibility of PD-1 and TIM-3 expression on T cells upon stimulation with commonγ-chain family cytokines in vitro and during homeostatic proliferation.The aim of the present work was to study the impact of homeostatic proliferation on the expansion of certain T cell subsets upregulating PD-1 and TIM-3 checkpoint molecules.Methods:The expression of CD25,CD122,CD127 commonγ-chain cytokine receptors,phosphorylated signal transducer and activator of transcription-5(pSTAT5)and eomesodermin(EOMES)was comparatively assessed with flow cytometry in PD-1-and TIM-3-negative and positive T cells before the conditioning and during the first post-transplant month in peripheral blood samples of MM patients.Results:Substantial proportions of PD-1-and TIM-3-positive T lymphocytes expressed commonγ-chain cytokine receptors and pSTAT5.Frequencies of cytokine receptor expressing cells were significantly higher within TIM-3+T cells compared to PD-1+TIM-3−subsets.Considerable proportions of both PD-1-/TIM-3-negative and positive CD8+T cells express EOMES,while only moderate frequencies of CD4+PD-1+/TIM-3+T cells up-regulate this transcription factor.Besides,the surface presence of CD25 and intranuclear expression of EOMES in CD4+T cells were mutually exclusive regardless of PD-1 and TIM-3 expression.The stimulation with commonγ-chain cytokines up-regulates PD-1 and TIM-3 during the proliferation of initially PD-1/TIM-3-negative T cells but fails to expand initially PD-1+and TIM-3+T cell subsets in vitro.Conclusions:Both PD-1 and TIM-3 expressing T cells appear to be able to respond to homeostatic cytokine stimulation.Differences in commonγ-chain cytokine receptor expression between PD-1+and TIM-3+T cells may reflect functional dissimilarity of these cell subsets.Checkpoint blockade appears to alleviate lymphopenia-induced proliferation of PD-1+T cells but may raise the possibility of immune-mediated adverse events.展开更多
为了保持电光调制器(EOM)输入光偏振方向始终与其内部可传播模式偏振方向一致,使EOM获得良好的调制效果,提出了一种基于比例-积分-微分(PID)算法的EOM自适应偏振控制方法,理论分析并实验验证了该方法的可行性。实验结果表明,基于该方法...为了保持电光调制器(EOM)输入光偏振方向始终与其内部可传播模式偏振方向一致,使EOM获得良好的调制效果,提出了一种基于比例-积分-微分(PID)算法的EOM自适应偏振控制方法,理论分析并实验验证了该方法的可行性。实验结果表明,基于该方法设计的控制系统不仅能实时监测EOM输出光功率,而且能保持其输出光功率最大;与激光器和EOM输入端直接用保偏光纤连接时相比,PID偏振控制下EOM输出平均功率提高了3.08 d B,PD输出电压标准差由0.121 4降至1.237 5×10-4,稳定控制状态下偏振态矫正时间在ms量级。展开更多
文摘Background:Immune checkpoint ligand-receptor interactions appear to be associated with multiple myeloma(MM)progression.Simultaneously,previous studies showed the possibility of PD-1 and TIM-3 expression on T cells upon stimulation with commonγ-chain family cytokines in vitro and during homeostatic proliferation.The aim of the present work was to study the impact of homeostatic proliferation on the expansion of certain T cell subsets upregulating PD-1 and TIM-3 checkpoint molecules.Methods:The expression of CD25,CD122,CD127 commonγ-chain cytokine receptors,phosphorylated signal transducer and activator of transcription-5(pSTAT5)and eomesodermin(EOMES)was comparatively assessed with flow cytometry in PD-1-and TIM-3-negative and positive T cells before the conditioning and during the first post-transplant month in peripheral blood samples of MM patients.Results:Substantial proportions of PD-1-and TIM-3-positive T lymphocytes expressed commonγ-chain cytokine receptors and pSTAT5.Frequencies of cytokine receptor expressing cells were significantly higher within TIM-3+T cells compared to PD-1+TIM-3−subsets.Considerable proportions of both PD-1-/TIM-3-negative and positive CD8+T cells express EOMES,while only moderate frequencies of CD4+PD-1+/TIM-3+T cells up-regulate this transcription factor.Besides,the surface presence of CD25 and intranuclear expression of EOMES in CD4+T cells were mutually exclusive regardless of PD-1 and TIM-3 expression.The stimulation with commonγ-chain cytokines up-regulates PD-1 and TIM-3 during the proliferation of initially PD-1/TIM-3-negative T cells but fails to expand initially PD-1+and TIM-3+T cell subsets in vitro.Conclusions:Both PD-1 and TIM-3 expressing T cells appear to be able to respond to homeostatic cytokine stimulation.Differences in commonγ-chain cytokine receptor expression between PD-1+and TIM-3+T cells may reflect functional dissimilarity of these cell subsets.Checkpoint blockade appears to alleviate lymphopenia-induced proliferation of PD-1+T cells but may raise the possibility of immune-mediated adverse events.
文摘为了保持电光调制器(EOM)输入光偏振方向始终与其内部可传播模式偏振方向一致,使EOM获得良好的调制效果,提出了一种基于比例-积分-微分(PID)算法的EOM自适应偏振控制方法,理论分析并实验验证了该方法的可行性。实验结果表明,基于该方法设计的控制系统不仅能实时监测EOM输出光功率,而且能保持其输出光功率最大;与激光器和EOM输入端直接用保偏光纤连接时相比,PID偏振控制下EOM输出平均功率提高了3.08 d B,PD输出电压标准差由0.121 4降至1.237 5×10-4,稳定控制状态下偏振态矫正时间在ms量级。
