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Adjuvant Effects of Dual Co-stimulatory Molecules on Cellular Responses to HIV Multiple-epitope DNA Vaccination 被引量:2
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作者 SHEN Zhen-wei JIN Hong-tao +4 位作者 LI Chang CONG Yan-zhao NAN Wen-long BAI Liang JIN Ning-yi 《Chemical Research in Chinese Universities》 SCIE CAS CSCD 2009年第3期347-352,共6页
Designing adjuvants that can induce strong cytotoxic T cell responses is largely required for preparing DNA vaccines. In this study we explored dual costimulatory molecules 4-1BBL and OX40L as adjuvants to improve the... Designing adjuvants that can induce strong cytotoxic T cell responses is largely required for preparing DNA vaccines. In this study we explored dual costimulatory molecules 4-1BBL and OX40L as adjuvants to improve the efficiency of the HIV multiple-epitope DNA vaccine. When explored in the human dendritic cell-T cell based coculture system, dual costimulatory molecules significantly enhanced the anti-HIV T cell response of the HIV multiple-epitope DNA vaccine, as detected by intracellular cytokine staining to HIV antigens, cytokines accumulation in the cultures, and antigen-specific cytotoxic T lymphocyte responses. These results suggest that dual costimulatory molecules 4-1BBL and OX40L can effectively increase the potential of the HIV multiple-epitope antigen DNA vaccine and may provide an exciting approach for HIV therapy. 展开更多
关键词 HIV DNA vaccine co-stimulatory molecules 4-1BBL OX40L Dendritic cells
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Expression of co-stimulatory molecules B7-2 and PD-L1 on peripheral blood mononuclear cells in patients with chronic hepatitis B virus infection
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作者 Lingxia Fei Shipin Wu Hongtao Chen 《Journal of Nanjing Medical University》 2009年第5期347-351,共5页
Objective: To explore the roles of the expression of the co-stimulatory molecule, B7-2, and the co-inhibitory molecule, PD-L1, on peripheral blood mononuclear cells in the mechanism of immunotolerance in chronic hepa... Objective: To explore the roles of the expression of the co-stimulatory molecule, B7-2, and the co-inhibitory molecule, PD-L1, on peripheral blood mononuclear cells in the mechanism of immunotolerance in chronic hepatitis B virus infection. Methods: Thirty HBV infected patients in the immunoreactive phase and 20 patients in the immunotolerant phase were enrolled in the study, while 20 healthy volunteers were used as controls. RT- PCR and real-time PCR methods were used to detect the expression levels of B7-2 and PD-L1 mRNA in peripheral blood mononuclear cells in chronic HBV infected patients. Results: The B7-2 expression in irnrnunoreactive and immunotolerant patients was significantly lower than that in the controls (P all 〈 0.01 ); B7-2 expression in immunoreactive patients was significantly lower than in immunotolerant patients (P 〈 0.01). PD-L1 expression in irnmunoreactive patients and immunotolerant patients was significantly higher than that in normal controls (P all 〈 0.01). The PD-L1/BT-2 ratios in immunoreactive and immunotolerant patients were significantly higher than that of the healthy controls (P all 〈 0.01); the PD-L1/ B7-2 ratio was significantly higher in the immunoreactive patients than in the immunotolerant patients (P 〈 0.01). Conclusion: In chronic HBV infection, changes in the expression of co-stimulatory and co-inhibitory molecules imply a protective adjustment against the patient' s immune response that may result in increased immunotolerance and persistent HBV infection. 展开更多
关键词 co-stimulatory molecule B7-2 PD-L1 Hepatitis B virus
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Estradiol regulates T cell activation by influencing co-stimulatory molecules transcription
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作者 SHI TING WANG YUN HOU +1 位作者 BEN LIU JIN LONG WANG 《Journal of Microbiology and Immunology》 2006年第3期237-244,共8页
To investigate whether estradiol (E2) plays a role in cell-contact-dependent regulatory mechanism of T cell activation, we studied the role of E2 in regulating gene transcription of CTLA-4, ICOS, B7-1, B7-2 and B7h ... To investigate whether estradiol (E2) plays a role in cell-contact-dependent regulatory mechanism of T cell activation, we studied the role of E2 in regulating gene transcription of CTLA-4, ICOS, B7-1, B7-2 and B7h in vitro. The splenic cells of normal female BALB/c mice were activated by ConA. Then the cells were cultured with E2 (100 pg/ml or 50 ng/ml) for 24 h or 48 h, respectively. The cell proliferation was measured by MTF assay and the expression of the co-stimulatory molecules mRNA was examined by RT-PCR analysis. We found that E2 (100 pg/ml, physiological level) stimulated the acti- vated spleen cells proliferation; inhibited CTLA-4, ICOS, TGF-β and IL-10 gene transcription; promoted B7-1 and B7-2 gene transcription. E2 (50 ng/ml, pregnant level) inhibited the proliferation of the activated splenic cells; promoted CTLA-4, B7-1, IL-10 but inhibited B7-2 and TGF-β gene transcription. Therefore, we conclude that the effects of E2 on T cell activation are partially through its regulation on the co-stimulatory molecules. The co-stimulatory molecules are crucial components of the cell-contact dependent regulatory mechanism, and E2 may regulate T cell activation by this mechanism. 展开更多
关键词 Estradiol (E2) T cell activation co-stimulatory molecules
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Research progress of ICOSL/ICOS pathway in maternal-fetal immune tolerance
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作者 MEI Jiao-qi YANG Xiao-hui +2 位作者 LIMENG Yong-wei MA Yan-lin HUANG Yuan-hua 《Journal of Hainan Medical University》 CAS 2023年第23期70-73,共4页
Co-signaling molecules are molecules whose ligands on the surface of cells interact with receptors on the surface of T cells to convey stimulatory or inhibitory signals to regulate immune responses.Co-signaling molecu... Co-signaling molecules are molecules whose ligands on the surface of cells interact with receptors on the surface of T cells to convey stimulatory or inhibitory signals to regulate immune responses.Co-signaling molecules play an important role in tumor and autoimmune diseases.Lately,studies have shown that co-signaling molecules are also involved in the regulation of maternal-fetal immune tolerance,and abnormalities of co-signaling molecules may lead to the imbalance of maternal-fetal immune tolerance,resulting in recurrent abortion,eclampsia and other pregnancy complications.ICOSL/ICOS is a ligand and receptor of costimulatory signals,which regulates maternal and fetal immune tolerance by participating in T cell differentiation and Th1 and Th2 cytokine secretion.Therefore,this article reviews the structure of ICOSL/ICOS,the distribution of ICOSL/ICOS at the maternal-fetal interface and its immune regulation during pregnancy,in order to provide new ideas for the future study of immunotherapy of pregnancy complications caused by abnormal co-signaling molecules. 展开更多
关键词 co-stimulatory molecules ICOSL/ICOS Immune tolerance TH1 TH2
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Probiotic metabolites from Bacillus coagulans GanedenBC30^(TM) support maturation of antigen-presenting cells in vitro 被引量:9
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作者 Kathleen F Benson Kimberlee A Redman +4 位作者 Steve G Carter David Keller Sean Farmer John R Endres Gitte S Jensen 《World Journal of Gastroenterology》 SCIE CAS CSCD 2012年第16期1875-1883,共9页
AIM:To study the effects of probiotic metabolites on maturation stage of antigen-presenting immune cells.METHODS:Ganeden Bacillus coagulans 30(GBC30) bacterial cultures in log phase were used to isolate the secreted m... AIM:To study the effects of probiotic metabolites on maturation stage of antigen-presenting immune cells.METHODS:Ganeden Bacillus coagulans 30(GBC30) bacterial cultures in log phase were used to isolate the secreted metabolite(MET) fraction.A second fraction was made to generate a crude cell-wall-enriched fraction,by centrifugation and lysis,followed by washing.A preparation of MET was subjected to size exclusion centrifugation,generating three fractions:< 3 kDa,3-30 kDa,and 30-200 kDa and activities were tested in comparison to crude MET and cell wall in primary cultures of human peripheral blood mononuclear cell(PBMC) as a source of antigen-presenting mononuclear phagocytes.The maturation status of mononuclear phagocytes was evaluated by staining with monoclonal antibodies towards CD14,CD16,CD80 and CD86 and analyzed by flow cytometry.RESULTS:Treatment of PBMC with MET supported maturation of mononuclear phagocytes toward both macrophage and dendritic cell phenotypes.The biological activity unique to the metabolites included a reduction of CD14+ CD16+ pro-inflammatory cells,and this property was associated with the high molecular weight metabolite fraction.Changes were also seen for the dendritic cell maturation markers CD80 and CD86.On CD14dim cells,an increase in both CD80 and CD86 expression was seen,in contrast to a selective increase in CD86 expression on CD14bright cells.The co-expression of CD80 and CD86 indicates effective antigen presentation to T cells and support of T helper cell differentiation.The selective expression of CD86 in the absence of CD80 points to a role in generating T regulatory cells.CONCLUSION:The data show that a primary mechanism of action of GBC30 metabolites involves support of more mature phenotypes of antigen-presenting cells,important for immunological decision-making. 展开更多
关键词 Mononuclear phagocytes Dendritic cell maturation co-stimulatory molecules Antigen-presentation PROBIOTICS METABOLITES
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Study of human B7 homolog 1 expression in patients with hepatitis B virus infection 被引量:1
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作者 Wen-Jin Zhang Hai-Yang Xie +8 位作者 Xin Duan Yun-Le Wan Chuan-Hui Peng Shao-Hua Shi Rong Su Zhang-Hui Zheng Le-Lin Pan Lin Zhou Shu-Sen Zheng 《World Journal of Gastroenterology》 SCIE CAS CSCD 2012年第28期3681-3695,共15页
AIM: To further investigate the role of human B7 homolog 1 (B7-H1) in the mechanism of persistent hepatitis B virus (HBV) infection. METHODS: Peripheral and intra-hepatic B7-H1 expression were compared by flow cytomet... AIM: To further investigate the role of human B7 homolog 1 (B7-H1) in the mechanism of persistent hepatitis B virus (HBV) infection. METHODS: Peripheral and intra-hepatic B7-H1 expression were compared by flow cytometry and immunochemical staining between two 2 distinct groups, one being chronic HBV tolerance patients (CHB-T) and the other being acute hepatitis B patients (AHB). B7-H1 mRNA expression level was also compared by real time polymerase chain reaction between CHB-T and AHB patients. The location of intra-hepatic B7-H1 and CD40 expression were analyzed by immunofluorescence. The levels of B7-H1 and CD40 expression on cultured myeloid dendritic cells (mDCs) with or without hepatitis B surface antigen (HBsAg) treatment were analyzed dynamically by flow cytometry. Intracellular interferon-γ (IFN-γ) staining and the stimulatory capacity of mDC of cultured mDC with or without HBsAg treatment were also compared by flow cytometry. RESULTS: Peripheral B7-H1 expression on mDCs was increased significantly in AHB compared to CHB-T patients (P < 0.05). In the liver tissues from CHB-T patients, B7-H1 positive cells were almost absent despite a persistently elevated serum HBsAg load. In contrast, there were indeed increased B7-H1-positive cells in situ in the liver tissue from AHB. In vitro analysis showed the parallel upregulation of B7-H1 and CD40 on CD11c+ mDCs after the onset of stimulation. Addition of recombinant hepatitis B surface antigen (rHBsAg) significantly decreased CD40 expression (P < 0.05 at 16 h, 20 h and 24 h time points). B7-H1 expression was also inhibited by rHBsAg, and the inhibition rate of CD40 was greater than that of B7-H1. This preferential inhibition of CD40 expression on mDCs by rHBsAg resulted in the dysfunction of mDCs and T cells in the mixed leucocyte reaction (MLR) system. With rHBsAg pretreatment, in a carboxyfluorescein diacetate succinimidyl ester (CFSE) labeled MLR system at a ratio of 1:5 responder cell-stimulator cell (R/S), the CFSE dim percentage of T cells decreased from 85.1% to 25.4% and decreased from 30.3% to 12.0% at 1:10 R/S. IFN-γ production by CD8+ T cells, in the MLR system, was reduced significantly by HBsAg pretreatment. At ratios of 1:5 R/S, the percentage of IFN-γ and CD8 dual positive T cells decreased from 55.2% ± 5.3% to 15.1% ±3.1% (P < 0.001), and decreased from 35.0% ± 5.1% to 7.3% ± 2.7% at ratios of 1:10 R/S (P < 0.001). CONCLUSION: B7-H1 is not a signature of immune dysfunction, but an inflammation marker. HBsAg regulate immune response by tipping the balance between B7-H1 and CD40. 展开更多
关键词 Hepatitis B virus Hepatitis B Human B7 homolog 1 Immune tolerance co-stimulatory molecule
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CAR T Cell Immunotherapy That Revolutionary Breakthrough in Human Oncology Treatment: A Review 被引量:1
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作者 Shammi Binte Bashar Zannat Akhter +3 位作者 Bidhan Chandro Saha Md. Mushfiqul Islam Himaloy Umme Kulsum Md. Rashedur Rahman 《Pharmacology & Pharmacy》 CAS 2022年第11期483-515,共33页
The discovery of CAR T cell immunotherapy, also known as chimeric antigen receptor (CAR) T cell immunotherapy, has added a new dimension to the world of cancer treatment. This is a gene-based treatment in which T cell... The discovery of CAR T cell immunotherapy, also known as chimeric antigen receptor (CAR) T cell immunotherapy, has added a new dimension to the world of cancer treatment. This is a gene-based treatment in which T cells from the patient’s body are taken and genetically engineered in the lab to grow receptors. T cells containing this receptor are then injected into the patient’s body to bind to the antigen on the surface area of the cancer cell and kill the cancer cell. Structurally, the co-stimulatory domain added to CAR T cells has now reached the 5<sup>th</sup> GEN of chimeric antigen receptor T cells. Chimeric antigen T cell immunotherapy is the first FDA-approved treatment for hematological malignancies that is both safe and effective. However, due to some challenges such as a lack of safety control, an immunosuppressive tumor microenvironment, ineffective T cell trafficking, and so on, CAR-T immunotherapy treatment for solid malignancy is still in the clinical phase. In the result and discussion, we have presented a survey of CAR T cell therapy with a combination of pharmacological drugs. The things we mentioned are that CAR T cell immunotherapy is innovative, suitable, elegant, and also controls synergistic anti-cancer effects. A better understanding of combinatory CAR T cell therapies provides fundamental information for improvement of those therapies, in addition to the article highlighting future opportunities, commercial advancements, and various applications of CAR T cell therapy in different cancer cells. In the entire review article, we have highlighted the neck and crop of CAR T cell therapy, from which it is easy to understand the therapy and the need for this therapy in cancer prevention and its progress. 展开更多
关键词 Cancer Immunotherapy Chimeric Antigen Receptor co-stimulatory Domain Cell Trafficking Hematological Malignancy
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Suppression of Allogeneic T Cells Proliferation by CD3/CD46-Induced T-regulatory 1 Cells
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作者 陈栋 张艳 +5 位作者 李明 张弛 陈刚 陈知水 陈实 张伟杰 《Journal of Huazhong University of Science and Technology(Medical Sciences)》 SCIE CAS 2010年第3期332-336,共5页
CD46 is not only identified as a complement regulatory protein which protects host cells from complement attack,but also a new co-stimulatory molecule for human T cells.CD3/CD46 co-stimulation can induce a T-regulator... CD46 is not only identified as a complement regulatory protein which protects host cells from complement attack,but also a new co-stimulatory molecule for human T cells.CD3/CD46 co-stimulation can induce a T-regulatory 1 cell(Tr1)-specific cytokine phenotype in human CD4+ T cells.However,the role of CD46 as a co-stimulatory molecule in the modulation of the acquired immunity,such as transplant immunology,remains unclear.In this study,CD4+ T cells were isolated from human CD46-transgenic C57BL/6 mice by magnetic-activated cell sorting,and further induced by anti-CD3,anti-CD28 and anti-CD46 antibodies respectively,and anti-CD3/anti-CD28 antibodies,anti-CD3/anti-CD46 antibodies,or the monoclonal antibody panel against CD3/CD28/CD46.The levels of interleukin-2(IL-2),γ-interferon(γ-IFN),interleukin-10(IL-10) and transforming growth factor-β(TGF-β) were detected in the supernatants of different groups.Suppression of allogeneic T cell proliferation were assessed by using mixed lymphocyte reaction(MLR) assay,in which monoclonal antibodies against CD46 were added to the culture.The results showed that CD3/CD28,CD3/CD46 and CD3/CD28/CD46 co-stimulation could significantly induce stronger proliferation of T cells than CD3 stimulation(P<0.05),and CD3/CD28/CD46 co-stimulation significantly increased the proliferation of T cells when compared with CD3/CD28 or CD3/CD46 co-stimulation(P<0.05 for each).IL-2 and γ-IFN levels were much higher in CD3/CD28 co-stimulation group than in CD3,CD28,CD46 and CD3/CD46 groups(P<0.05 for each).IL-10 and TGF-β levels were dramatically increased in CD3/CD46 co-stimulation group as compared with those in the CD3,CD28,CD46 and CD3/CD28 groups(P<0.05 for each).CD3/CD46 co-stimulation significantly inhibited the T cell proliferation and allogenic immune responses through the secretion of IL-10 and TGF-β in MLR(P<0.05).These results suggested that CD3/CD46 can induce Tr1 cells to modulate allogenic immune responses,and it may become a novel target for the development of new therapeutic approach for T-cell-mediated diseases.CD46 plays an important role in regulating the T cell-mediated immune responses by bridging innate and acquired immunity. 展开更多
关键词 CD46 co-stimulatory molecule T-regulatory 1 cells allogenic immune response
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Expression of Inducible Co-stimulator in Peripheral Blood T Lymphocytes in the Patients with Systemic Lupus Erythematosus
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作者 陈志平 刘贞富 +1 位作者 郑舜华 梁智辉 《Journal of Huazhong University of Science and Technology(Medical Sciences)》 SCIE CAS 2005年第3期357-359,共3页
The expression of inducible co-stimulator (ICOS) in peripheral blood T lymphocytes from the patients with systemic lupus erythematosus (SLE) and the role in the pathogenesis of SLE was investigated. By using two-color... The expression of inducible co-stimulator (ICOS) in peripheral blood T lymphocytes from the patients with systemic lupus erythematosus (SLE) and the role in the pathogenesis of SLE was investigated. By using two-color immunofluorescent staining and flow cytometric assay, the expression levels of ICOS in peripheal blood T lymphocytes from 33 patients with SLE and 16 healthy volunteers were detected. SLE diseases activity index (SLEDAI) of the patients with SLE was used to evaluate the disease activity. The correlation between the ICOS expression and SLEDAI was analyzed among the groups. The results showed that the expression levels of ICOS in T lymphocytes in active SLE group was markedly higher than those in the control and inactive SLE groups (both P<0.01). There was no significant difference in the expression levels of ICOS between the inactive SLE and the control groups (P>0.05). In active SLE and inactive SLE groups, positive linear correlation was found between the levels of the ICOS expression in T lymphocytes and SLEDAI (r=0.711, P=0.001; r=0.561, P=0.03). It was suggested that the expression of ICOS in peripheral blood T lymphocytes from the patients with active SLE was up-regulated and and ICOS might be related to the pathogenesis of SLE. 展开更多
关键词 lupus erythematosus systemic inducible co-stimulatory
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Historical evolution,overview,and therapeutic manipulation of costimulatory molecules
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作者 Henry Velazquez-Soto Fernanda Real Maria C Jimenez-Martinez 《World Journal of Immunology》 2022年第1期1-8,共8页
Co-stimulatory molecules are key mediators in the regulation of immune responses and knowledge of its different families,structure,and functions has improved in recent decades.Understanding the role of co-stimulatory ... Co-stimulatory molecules are key mediators in the regulation of immune responses and knowledge of its different families,structure,and functions has improved in recent decades.Understanding the role of co-stimulatory molecules in pathological processes has allowed the development of strategies to modulate cellular functions.Currently,modulation of co-stimulatory and co-inhibitory molecules has been applied in clinical applications as therapeutic targets in diseases and promising results have been achieved. 展开更多
关键词 co-stimulatory molecules Immune modulation Monoclonal antibodies Biological therapy Autoimmune diseases Oncological diseases
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High dimensional proteomic mapping of bone marrow immune characteristics in immune thrombocytopenia
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作者 Feng-Qi Liu Qing-Yuan Qu +12 位作者 Ying Lei Qi Chen Yu-Xiu Chen Meng-Lin Li Xue-Yan Sun Ye-Jun Wu Qiu-Sha Huang Hai-Xia Fu Yuan Kong Yue-Ying Li Qian-Fei Wang Xiao-Jun Huang Xiao-Hui Zhang 《Science China(Life Sciences)》 SCIE CAS CSCD 2024年第8期1635-1647,共13页
To investigate the role of co-stimulatory and co-inhibitory molecules on immune tolerance in immune thrombocytopenia(ITP),this study mapped the immune cell heterogeneity in the bone marrow of ITP at the single-cell le... To investigate the role of co-stimulatory and co-inhibitory molecules on immune tolerance in immune thrombocytopenia(ITP),this study mapped the immune cell heterogeneity in the bone marrow of ITP at the single-cell level using Cytometry by Time of Flight(CyTOF).Thirtysix patients with ITP and nine healthy volunteers were enrolled in the study.As soluble immunomodulatory molecules,more sCD25 and sGalectin-9 were detected in ITP patients.On the cell surface,co-stimulatory molecules like ICOS and HVEM were observed to be upregulated in mainly central memory and effector T cells.In contrast,co-inhibitory molecules such as CTLA-4 were significantly reduced in Th1 and Th17 cell subsets.Taking a platelet count of 30×10^(9)L^(−1)as the cutoff value,ITP patients with high and low platelet counts showed different T cell immune profiles.Antigen-presenting cells such as monocytes and B cells may regulate the activation of T cells through CTLA-4/CD86 and HVEM/BTLA interactions,respectively,and participate in the pathogenesis of ITP.In conclusion,the proteomic and soluble molecular profiles brought insight into the interaction and modulation of immune cells in the bone marrow of ITP.They may offer novel targets to develop personalized immunotherapies. 展开更多
关键词 immune thrombocytopenia autoimmune diseases co-stimulatory co-inhibitory immune checkpoint CTLA4 Cytometry by Time of Flight bone marrow
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