CD40L-CD40 interaction is central to the control of thymusdependent humoral immunity and cell mediated immune responses. CD40, a member of the tumor necrosis factor receptor （TNF- R） family, has been found on the su...CD40L-CD40 interaction is central to the control of thymusdependent humoral immunity and cell mediated immune responses. CD40, a member of the tumor necrosis factor receptor （TNF- R） family, has been found on the surface of B lymphocytes, monocytes, hematopoietic progenitors, dendritic cells （DCs）, endothelial cells, epithelial cells and so on. Its natural ligand （CD40 ligand, CD40L）, CD154, a member of the tumor necrosis factor （TNF） family, is mainly expressed on activated CD4^＋ T lymphocytes. A direct growth-inhibitory effect can be found when ligated CD40 is on human breast, ovarian, cervical, bladder, non-small cell lung, and squamous epithelial carcinoma cells. This effect is related to the induction of cell cycle blockage and/or apoptosis. CD40L induces phenotypic and functional maturation of DCs, and can increase tumor immunogenicity through up-regulation of costimulatory molecular expression and cytokine production by epithelial cancer cells. As a result, CD40L can enhance tumor rejection immune responses. Furthermore, by means of a “bystander effect”, even CD40-negative tumor subsets can be eliminated by activated tumor-reactive cytotoxic T lymphocytes（CTL）. This review summarizes recent findings on CD40L recombinant protein and gene therapy-based tumor treatment approaches.展开更多
Hyper IgM syndrome is a rare immunodeficiency disease characterized by low or absent IgG, IgA, and IgE levels but normal or elevated level of IgM. It can occur as an acquired form or X linked or autosomal mode of in...Hyper IgM syndrome is a rare immunodeficiency disease characterized by low or absent IgG, IgA, and IgE levels but normal or elevated level of IgM. It can occur as an acquired form or X linked or autosomal mode of inheritance. The X linked form (HIGM1) is a result of mutations in the CD40L ligand (CD40L) gene. We investigate the expression of CD40L on activated T cells from a sporadic male case of HIM with no family history and the B cell function in response to anti CD40L mAb and cytokines. Staining of CD40L on activated T cells from the patient is negative with recently developed anti human CD40L mAb, M90 and M92. The low expression of CD40L on activated T cells from the patient′s mother is also detected. Sequencing of CD40L coding region reveals a 4 bp deletion within the CD40L binding domain. These results indicate that the patient has X linked inheritance pattern (XIGM1). CD40L mAb alone could induce the patient′s PBMCs to secret markedly IgG. Our data suggest that the detection of CD40L expression on ativated T cells may be used to identify sporadic cases of HIM as HIGM1.展开更多
Objective： To investigate the expression of CD40 and CD40 ligand （CD4OL） on the surface of peripheral blood mononuclear cells（PBMCs） in asthmatic rats and the effect of anti-CD40L McAb on cytokines of PBMCs. Meth...Objective： To investigate the expression of CD40 and CD40 ligand （CD4OL） on the surface of peripheral blood mononuclear cells（PBMCs） in asthmatic rats and the effect of anti-CD40L McAb on cytokines of PBMCs. Methods： Flow cytometry and RT-PCR were used to detect the expression of CD40 and CD40L of PBMCs in asthmatic rats. After the PBMCs was treated with anti-CD40L McAb, ELISA was used to detect the IL-4 and IFN-γ levels of culture supernatants. Results： Compared with the normal control group, the expression of CD40 and CD40L of PBMCs in asthmatic rats increased （P 〈 0.05）. Compared with the untreated group, the level of IL-γ and the ratio of IL-4/IFN-γ decreased after the PBMCs was treated with anti-CD40L McAb（P 〈 0.05）. Conclusion： The expression of CD40 and CD40L on the surface of PBMCs in asthmatic rats was up-regulated. Anti-CD40L McAb can rectify the imbalance of Th1 and Th2 cytokines.展开更多
Objective:Toanalyze the effect of PCI treatment on blood WBC(White blood cell),CD40 L and cTnI(Cardiac Troponin I)levels and prognosis in patients with ST segment elevation myocardial infarction combined with arrhythm...Objective:Toanalyze the effect of PCI treatment on blood WBC(White blood cell),CD40 L and cTnI(Cardiac Troponin I)levels and prognosis in patients with ST segment elevation myocardial infarction combined with arrhythmia at different time windows.Methods 87 patients with arrhythmia who were treated from January 2017 to January 2019 were seleted as the research objects.They were divided into≤3 h group,3 to 6 h group,and 6 to 12 h group according to the PCI treatment time window.Patients were treated by PCI in all groups.The recanalization and reperfusion arrhythmia of patients after vascular occlusion were investigated.The WBC,cTnI,and CD40 L levels in patients'serum were measured at the time of enrollment and 24 hours after the end of treatment.Result The vascular recanalization rate was significantly different in the three groups,and the difference was statistically significant(P<0.05).The vascular recanalization rate was the highest in the≤3 h group and the lowest in the 6-12 h group.There was a significant difference in the incidence of reperfusion arrhythmia among the three groups(P<0.05),of which the incidence rate was the highest in the≤3 h group,and the time of the occurrence of reperfusion arrhythmia in the three groups was significantly different,and the difference was statistically significant(P<0.05).The time of the occurrence of reperfusion arrhythmia was highest in the 6-12 h group,there was no significant difference in time between the≤3 h group and the 3-6 h group(P>0.05.There were significant differences in WBC,CD40L and cTnI levels in the three groups,and the differences were statistically significant(P<0.05).The serum WBC,CD40L and cTnI levels were highest in≤3 h group,but there was no significant difference in WBC,CD40L and cTnI levels in the 3-6 h group and 6-12 group.Conclusion The best time window of PCI treatment is 3~6h in patients with arrhythmia,which can significantly improve the levels of serum WBC,CD40L and cTnI.展开更多
文摘CD40L-CD40 interaction is central to the control of thymusdependent humoral immunity and cell mediated immune responses. CD40, a member of the tumor necrosis factor receptor （TNF- R） family, has been found on the surface of B lymphocytes, monocytes, hematopoietic progenitors, dendritic cells （DCs）, endothelial cells, epithelial cells and so on. Its natural ligand （CD40 ligand, CD40L）, CD154, a member of the tumor necrosis factor （TNF） family, is mainly expressed on activated CD4^＋ T lymphocytes. A direct growth-inhibitory effect can be found when ligated CD40 is on human breast, ovarian, cervical, bladder, non-small cell lung, and squamous epithelial carcinoma cells. This effect is related to the induction of cell cycle blockage and/or apoptosis. CD40L induces phenotypic and functional maturation of DCs, and can increase tumor immunogenicity through up-regulation of costimulatory molecular expression and cytokine production by epithelial cancer cells. As a result, CD40L can enhance tumor rejection immune responses. Furthermore, by means of a “bystander effect”, even CD40-negative tumor subsets can be eliminated by activated tumor-reactive cytotoxic T lymphocytes（CTL）. This review summarizes recent findings on CD40L recombinant protein and gene therapy-based tumor treatment approaches.
文摘Hyper IgM syndrome is a rare immunodeficiency disease characterized by low or absent IgG, IgA, and IgE levels but normal or elevated level of IgM. It can occur as an acquired form or X linked or autosomal mode of inheritance. The X linked form (HIGM1) is a result of mutations in the CD40L ligand (CD40L) gene. We investigate the expression of CD40L on activated T cells from a sporadic male case of HIM with no family history and the B cell function in response to anti CD40L mAb and cytokines. Staining of CD40L on activated T cells from the patient is negative with recently developed anti human CD40L mAb, M90 and M92. The low expression of CD40L on activated T cells from the patient′s mother is also detected. Sequencing of CD40L coding region reveals a 4 bp deletion within the CD40L binding domain. These results indicate that the patient has X linked inheritance pattern (XIGM1). CD40L mAb alone could induce the patient′s PBMCs to secret markedly IgG. Our data suggest that the detection of CD40L expression on ativated T cells may be used to identify sporadic cases of HIM as HIGM1.
文摘Objective： To investigate the expression of CD40 and CD40 ligand （CD4OL） on the surface of peripheral blood mononuclear cells（PBMCs） in asthmatic rats and the effect of anti-CD40L McAb on cytokines of PBMCs. Methods： Flow cytometry and RT-PCR were used to detect the expression of CD40 and CD40L of PBMCs in asthmatic rats. After the PBMCs was treated with anti-CD40L McAb, ELISA was used to detect the IL-4 and IFN-γ levels of culture supernatants. Results： Compared with the normal control group, the expression of CD40 and CD40L of PBMCs in asthmatic rats increased （P 〈 0.05）. Compared with the untreated group, the level of IL-γ and the ratio of IL-4/IFN-γ decreased after the PBMCs was treated with anti-CD40L McAb（P 〈 0.05）. Conclusion： The expression of CD40 and CD40L on the surface of PBMCs in asthmatic rats was up-regulated. Anti-CD40L McAb can rectify the imbalance of Th1 and Th2 cytokines.
基金Science and Technology Project of Hubei Provincial Department of Education(No.2017112)General Project of Hubei Provincial Department of Science and Technology(No.2018CFB537)
文摘Objective:Toanalyze the effect of PCI treatment on blood WBC(White blood cell),CD40 L and cTnI(Cardiac Troponin I)levels and prognosis in patients with ST segment elevation myocardial infarction combined with arrhythmia at different time windows.Methods 87 patients with arrhythmia who were treated from January 2017 to January 2019 were seleted as the research objects.They were divided into≤3 h group,3 to 6 h group,and 6 to 12 h group according to the PCI treatment time window.Patients were treated by PCI in all groups.The recanalization and reperfusion arrhythmia of patients after vascular occlusion were investigated.The WBC,cTnI,and CD40 L levels in patients'serum were measured at the time of enrollment and 24 hours after the end of treatment.Result The vascular recanalization rate was significantly different in the three groups,and the difference was statistically significant(P<0.05).The vascular recanalization rate was the highest in the≤3 h group and the lowest in the 6-12 h group.There was a significant difference in the incidence of reperfusion arrhythmia among the three groups(P<0.05),of which the incidence rate was the highest in the≤3 h group,and the time of the occurrence of reperfusion arrhythmia in the three groups was significantly different,and the difference was statistically significant(P<0.05).The time of the occurrence of reperfusion arrhythmia was highest in the 6-12 h group,there was no significant difference in time between the≤3 h group and the 3-6 h group(P>0.05.There were significant differences in WBC,CD40L and cTnI levels in the three groups,and the differences were statistically significant(P<0.05).The serum WBC,CD40L and cTnI levels were highest in≤3 h group,but there was no significant difference in WBC,CD40L and cTnI levels in the 3-6 h group and 6-12 group.Conclusion The best time window of PCI treatment is 3~6h in patients with arrhythmia,which can significantly improve the levels of serum WBC,CD40L and cTnI.
