The 8^th International Workshop on Human Leucocyte Differentiation Antigens (chaired by HZ and managed by BS) was run over a 4-year period and culminated in a conference in December 2004. Here we review the achievem...The 8^th International Workshop on Human Leucocyte Differentiation Antigens (chaired by HZ and managed by BS) was run over a 4-year period and culminated in a conference in December 2004. Here we review the achievements of the HLDA Workshops and provide links to information on CD molecules and antibodies against them, including the 93 new CDs assigned in the 8^th Workshop. We consider what remains to be achieved (including an estimate of the number of leucocyte surface molecules still to be discovered), and how the field can best move forward.展开更多
Objective: To investigate the effects of CD137 signaling on the regulation of CD3-CD56+NK cells function. Methods: CD3 CD56+NK cells were treated with CD137 mAb or mouse IgG 1 isotype control to study the effects ...Objective: To investigate the effects of CD137 signaling on the regulation of CD3-CD56+NK cells function. Methods: CD3 CD56+NK cells were treated with CD137 mAb or mouse IgG 1 isotype control to study the effects of CD 137 signaling on the function of CD3-CD56+NK cells. Cytotoxicity was measured by LDH activity in the supernatants of cell cultures; NKG2D and LFA-I expression on CD3-CD56+NK cells were analyzed by flow cytometry. Results: CD137 was expressed on activated CD3-CD56+NK cells. The CD137 mAb enhanced the ability of CDB-CD56+NK cells to kill lung cancer cells(A549); Further studies revealed that the expression of NKG2D and LFA-1 was significantly increased in activated cells, and blockade of NKG2D and LFA-1 dramatically attenuated CD3CD56+NK cytolysis of A549 cancer cells. Conclusion: CD 137 signaling increases the ability of CD3-CD56+NK cells to kill cancer cells via up- regulating the expression of NKG2D and LFA-1.展开更多
BACKGROUND The inflammatory response caused by the NLRP3 is closely related to the formation of myocardial ischemiareperfusion injury.Costimulatory receptor CD137 and its ligand play a crucial role in regulating the i...BACKGROUND The inflammatory response caused by the NLRP3 is closely related to the formation of myocardial ischemiareperfusion injury.Costimulatory receptor CD137 and its ligand play a crucial role in regulating the inflammatory immune response in atherosclerosis,which is the fundamental cause of cardiovascular diseases.However,the roles of CD137 signaling in the process of myocardial ischaemia-reperfusion(IR)injury remain unknown.METHODS Genetic ablation was used to determine the functional significance of CD137 in myocardial IR injury.Expression of CD137 was examined by Western-blot,quantitative real-time polymerase chain reaction,and immunohistochemistry in a murine IR model by coronary artery ligation.Even’s blue-TTC staining and echocardiography to evaluate the severity of myocardial IR injury.Furthermore,HL-1 cardiomyocytes treated with agonist-CD137 recombinant protein were used to explore the underlying mechanism in CD137 signaling-induced NLRP3 inflammasome activation in response to hypoxia/reoxygenation or LPS/ATP.RESULTS We demonstrated that CD137 knockout significantly improved cardiac function,accompanied by a markedly reduced NLRP3-mediated inflammatory response and IA/AAR which were reversed by mitophagy inhibitor Mdivi-1.Activating CD137 signaling significantly inhibited mitophagy and provoked NLRP3-mediated inflammatory response in H/R-injured or LPS-primed and ATP-stimulated HL-1 cardiomyocytes,the effects of which could be abolished by either anti-CD137 or mitophagy activator FCCP.Besides,mitochondrial ROS was augmented by activating CD137 signaling through the suppression of mitophagy.CONCLUSIONS Our results reveal that activating CD137 signaling aggravates myocardial IR injury by upregulating NLRP3 inflammasome activation via suppressing mitophagy and promoting mtROS generation.展开更多
CD137 (TNFRSF9,4-1BB) is a member of the tumor necrosis factor (TNF) receptor family and a potent costimulatory molecule.High levels of CD137 are expressed on T cells upon activation.CD137 signaling in T cells,either ...CD137 (TNFRSF9,4-1BB) is a member of the tumor necrosis factor (TNF) receptor family and a potent costimulatory molecule.High levels of CD137 are expressed on T cells upon activation.CD137 signaling in T cells,either by cognate interaction with antigen-presenting cells (APC)or by agonistic anti-CD137 antibodies,strongly enhances proliferation,interferon-y secretion,and cytolytic activity of T cells.Thus,CD137 signaling is a main driver of cellular,type 1 helper T cells (Th1)and type 1 cytolytic T cells (Tc1) polarised immune responses.展开更多
文摘The 8^th International Workshop on Human Leucocyte Differentiation Antigens (chaired by HZ and managed by BS) was run over a 4-year period and culminated in a conference in December 2004. Here we review the achievements of the HLDA Workshops and provide links to information on CD molecules and antibodies against them, including the 93 new CDs assigned in the 8^th Workshop. We consider what remains to be achieved (including an estimate of the number of leucocyte surface molecules still to be discovered), and how the field can best move forward.
基金supported by National Nature Science Foundation of China (No.30772549)
文摘Objective: To investigate the effects of CD137 signaling on the regulation of CD3-CD56+NK cells function. Methods: CD3 CD56+NK cells were treated with CD137 mAb or mouse IgG 1 isotype control to study the effects of CD 137 signaling on the function of CD3-CD56+NK cells. Cytotoxicity was measured by LDH activity in the supernatants of cell cultures; NKG2D and LFA-I expression on CD3-CD56+NK cells were analyzed by flow cytometry. Results: CD137 was expressed on activated CD3-CD56+NK cells. The CD137 mAb enhanced the ability of CDB-CD56+NK cells to kill lung cancer cells(A549); Further studies revealed that the expression of NKG2D and LFA-1 was significantly increased in activated cells, and blockade of NKG2D and LFA-1 dramatically attenuated CD3CD56+NK cytolysis of A549 cancer cells. Conclusion: CD 137 signaling increases the ability of CD3-CD56+NK cells to kill cancer cells via up- regulating the expression of NKG2D and LFA-1.
基金supported as follows:National Natural Science Foundation of China(81970379)Postgraduate Research&Practice Innovation Program of Jiangsu Province(KYCX22_3712)Medical Innovation Team Project of Jiangsu Province(CXTDA2017010).
文摘BACKGROUND The inflammatory response caused by the NLRP3 is closely related to the formation of myocardial ischemiareperfusion injury.Costimulatory receptor CD137 and its ligand play a crucial role in regulating the inflammatory immune response in atherosclerosis,which is the fundamental cause of cardiovascular diseases.However,the roles of CD137 signaling in the process of myocardial ischaemia-reperfusion(IR)injury remain unknown.METHODS Genetic ablation was used to determine the functional significance of CD137 in myocardial IR injury.Expression of CD137 was examined by Western-blot,quantitative real-time polymerase chain reaction,and immunohistochemistry in a murine IR model by coronary artery ligation.Even’s blue-TTC staining and echocardiography to evaluate the severity of myocardial IR injury.Furthermore,HL-1 cardiomyocytes treated with agonist-CD137 recombinant protein were used to explore the underlying mechanism in CD137 signaling-induced NLRP3 inflammasome activation in response to hypoxia/reoxygenation or LPS/ATP.RESULTS We demonstrated that CD137 knockout significantly improved cardiac function,accompanied by a markedly reduced NLRP3-mediated inflammatory response and IA/AAR which were reversed by mitophagy inhibitor Mdivi-1.Activating CD137 signaling significantly inhibited mitophagy and provoked NLRP3-mediated inflammatory response in H/R-injured or LPS-primed and ATP-stimulated HL-1 cardiomyocytes,the effects of which could be abolished by either anti-CD137 or mitophagy activator FCCP.Besides,mitochondrial ROS was augmented by activating CD137 signaling through the suppression of mitophagy.CONCLUSIONS Our results reveal that activating CD137 signaling aggravates myocardial IR injury by upregulating NLRP3 inflammasome activation via suppressing mitophagy and promoting mtROS generation.
文摘CD137 (TNFRSF9,4-1BB) is a member of the tumor necrosis factor (TNF) receptor family and a potent costimulatory molecule.High levels of CD137 are expressed on T cells upon activation.CD137 signaling in T cells,either by cognate interaction with antigen-presenting cells (APC)or by agonistic anti-CD137 antibodies,strongly enhances proliferation,interferon-y secretion,and cytolytic activity of T cells.Thus,CD137 signaling is a main driver of cellular,type 1 helper T cells (Th1)and type 1 cytolytic T cells (Tc1) polarised immune responses.