Colon cancer is still one of the leading causes of cancer death worldwide. Although the host immune system has been shown to react against tumor cells, mainly through tumor infi ltrating lymphocytes and NK cells, tumo...Colon cancer is still one of the leading causes of cancer death worldwide. Although the host immune system has been shown to react against tumor cells, mainly through tumor infi ltrating lymphocytes and NK cells, tumor cells may utilize different ways to escape anti-tumor immune response. Tumor infi ltration of CD8+ and CD4+ (T-bet+) effector T cells has been attributed to a beneficial outcome, and the enhancement of T cell activation through T cell receptor stimulation and co-stimulatory signals provides promising strategies for immunotherapy of colon cancer. Growing evidence supports a role for the Fas/FasL system in tumor immunology, although the mechanisms and consequences of FasL activation in colon cancer are not completely understood. In animal models, depletion of regulatory T cells (CD4+ CD25+ T cells) can enhance the anti-tumor immune response under certain conditions. Taken together, recent insights in the immune reaction against colon carcinoma have provided new approaches to immunotherapy, although much remains to be learned about the exact mechanisms.展开更多
Objective: To investigate the effect and clinical significance of Xuebijing injection on peripheral T-lymphocyte subpopulations in patients with severe trauma. Methods: Thirty-three patients with severe trauma were...Objective: To investigate the effect and clinical significance of Xuebijing injection on peripheral T-lymphocyte subpopulations in patients with severe trauma. Methods: Thirty-three patients with severe trauma were randomly divided into a control group (n=16) and a treatment group (n=17). The patients of two groups were all treated conventionally, and the only difference was that Xuebijing injection was given to patients of the treatment group. The CD4^+ and CD8^+ subpopulations of T-lymphocyte in the peripheral blood were detected respectively on admission, 3rd and 5th days after trauma by double antibody labeling and flow cytometry. Results: The CD4^+ T-lymphocytes and CD4^+/CD8^+ ratio of peripheral blood in patients with severe trauma decreased markedly on the 3rd and 5th days after trauma. Furthermore, compared with control group, the peripheral CD4^+ T-lymphocytes and CD4^+/CD8^+ ratio of treatment group renewed obviously on the 5th day after trauma, and showed statistical differences (P〈0.05). Conelusion: In the treatment of patients with severe trauma, the early use of Xuebijing injection is effective in correcting disorder or suppression of T-lymphocyte subpopulations regulating network, and promoting a more balanced profile of immunologic function.展开更多
OBJECTIVE: To investigate the compositions of Th1/Th2/Th3 cells in chronic hepatitis B virus (HBV)-infected individuals by determining the expression of interleukin-4 (IL-4), inetrferon-gamma (IFN-gamma), and transfor...OBJECTIVE: To investigate the compositions of Th1/Th2/Th3 cells in chronic hepatitis B virus (HBV)-infected individuals by determining the expression of interleukin-4 (IL-4), inetrferon-gamma (IFN-gamma), and transform growth factor-beta (TGF-beta) in single CD4(+) T cells isolated from peripheral blood mononuclear cells (PBMCs) and the role of polarized Th cell populations in chronic HBV-infection was discussed. METHODS: PBMCs from chronically infected HBV individuals were isolated, stimulated by PMA/Ionomycin/Monensin, and IL-4, IFN-gamma and TGF-beta production by CD4(+) T cells was determined by using fluorescence activated cell sorter (FACS) analysis. RESULTS: The percentage of IFN-gamma-producing T cells, IL-4-producing T cells and TGF-beta-producing T cells ranged from 2.3% - 18.6%, 1.1% - 8.7% and 0.7% - 7.1% respectively in CD4(+) T cells from non-infected individuals. Most of CD4(+) T cells from PBMCs in chronically infected HBV individuals were Th0 cells. The proportion of Th1 cells increased significantly with hepatic inflammatory activity, and in the active period of chronic hepatitis B infection were higher than those in the non-active period (P 0.05), but were higher than that from controls (P展开更多
Background Hemorrhagic shock induces immune dysfunction. Regulatory T cells (Tregs), T-helper (Th) cells, and cytotoxic T-lymphocytes (CTLs) can execute many crucial actions in immune and inflammatory responses....Background Hemorrhagic shock induces immune dysfunction. Regulatory T cells (Tregs), T-helper (Th) cells, and cytotoxic T-lymphocytes (CTLs) can execute many crucial actions in immune and inflammatory responses. This study was conducted to investigate the early pathophysiological changes of CD4+CD25+Foxp3+ Treg and Th1/Th2, Tc1/Tc2 profiles in the peripheral blood of rats with controlled hemorrhagic shock and no fluid resuscitation. Methods A rat model of controlled hemorrhagic shock with no fluid resuscitation was established. Peripheral blood samples were taken before and four hours after hemorrhagic shock with no fluid resuscitation. Three color flow cytometry was used to detect Tregs, Thl, Th2, Tcl and Tc2 ceils in the samples. Results In the peripheral blood of rats, the percentage of Tregs four hours after hemorrhagic shock was significantly lower than before hemorrhagic shock (P=0.001). The ratios of Th1/Th2 and Tc1/Tc2 were changed from (23.08±8.98)% to (23.91±15.36)%, and from (40.40±21.56)% to (65.48±23.88)%, respectively. Conclusions At an early stage, the advent of hemorrhagic shock is related to an early decrease of Tregs, and a mild shift in the Th1/Th2, Tc1/Tc2 balance toward Thl and Tcl dominance. These changes are part of a hyper-inflammatory state of the host, and will deteriorate the maintenance of immune balance. Further influences and detailed mechanisms need to be investigated.展开更多
OBJECTIVE: To establish a serum-free culture system of dendritic cells (DCs) from chronic myeloid leukemia (CML) cells so that DCs vaccine may be applied to the adoptive immunotherapy of CML in the near future. METHOD...OBJECTIVE: To establish a serum-free culture system of dendritic cells (DCs) from chronic myeloid leukemia (CML) cells so that DCs vaccine may be applied to the adoptive immunotherapy of CML in the near future. METHODS: Fetal calf serum, serum-free medium and autologous serum were used for culture of DCs. The usage of cytokines was classified into two groups: group A (stem cell factor, granulocyte/macrophage colony-stimulating-factor, tumor necrosis factor-alpha and interleukin-4) and group B (granulocyte/macrophage colony-stimulating-factor, tumor necrosis factor-alpha and interleukin-4). The phenotypes of DCs were analyzed by using indirect immunofluorescence and flow cytometry. Mixed leukocyte responses were performed by methyl thiazolyl tetrazolium (MTT) assay. Chromosome analysis of DCs can be achieved by displaying G banding. T cells from CML patients were stimulated with autologous DCs and T-cell cytotoxicity was measured by (MTT) assay. RESULTS: CD34(+) cells or mononuclear cells were obtained from peripheral blood or bone marrow samples of eight patients of chronic-phase CML. Group A of serum-free medium was better than group B in expansion of total cell numbers and the rate of DCs. These results of serum-free medium were not significantly different from those of fetal calf serum medium, but the results of autologous serum medium were inferior to two groups above. The expression of major histocompatibility complex class II antigen on the surface of DCs was notable (> 50%), but the expression of CD83 and the costimulatory molecules CD86 was not noticeable (10% - 50%). Although CD1a(+)/CD14(-) DCs were potent stimulators of allogeneic lymphocytes, expansion of T cells from normal volunteers were not significant (average 27.2 fold at DCs: T cells ratio of 1:10). At day 12, CD1a(+) cells from three patients were studied by displaying G banding and Ph(+) cells in these populations were 100%, 98% and 60%, respectively. At an effector: target ratio of 40:1, 32% to 45% cytotoxicity was noted with DC-stimulated T cells against autologous leukemia cells. CONCLUSIONS: A stable serum-free culture system of CML-DCs was established. The expression of CD83 and CD86 on the surface of CML-DCs and DCs' potent stimulation of allogeneic lymphocytes were not notable. DCs in CML patients can be derived from the malignant clone and these malignant DCs could induce anti-leukemic reactivity in autologous T lymphocytes without the necessity for additional exogenous antigens.展开更多
OBJECTIVE:To evaluate the effectiveness of Xiaoyin Jiedu(XYJD)granules in the treatment of psoriasis vulgaris(PSV)in patients with a blood-heat pattern(BHP)in terms of Traditional Chinese Medicine(TCM).We also aimed t...OBJECTIVE:To evaluate the effectiveness of Xiaoyin Jiedu(XYJD)granules in the treatment of psoriasis vulgaris(PSV)in patients with a blood-heat pattern(BHP)in terms of Traditional Chinese Medicine(TCM).We also aimed to identify the possible underlying immunological mechanism.METHODS:Twenty-five PSV patients with BHP and ten normal controls were enrolled from January 1,2015 to December 31,2016.Patients were randomly assigned to either the XYJD group(15 cases)or the placebo group(10 cases),in which patients were treated with XYJD granules or a placebo,respectively.Additionally,albolene was used to relieve skin dryness in these two groups.The psoriasis area and severity indexes,dermatology life quality indexes and itching scores were assessed at the end of the 2 nd,4 th and 8 th week of treatment.The number of peripheral blood T helper(Th)9,Th17 and regulatory T cells(Tregs)and the m RNA and protein expression levels of PU.1,RAR-related orphan receptor(ROR)-γt,forkhead box protein 3(Foxp3),interleukin(IL)-9,IL-17,IL-23 and IL-10 in the control and experimental groups were compared before and after treatment.RESULTS:Psoriasis area and severity indexes and itching scores of patients in the XYJD group were significantly lower than those in the placebo group,whereas dermatology life quality indexes were significantly higher.In comparison with the placebo group,XYJD granules significantly reduced the number of Th17 cells and the m RNA and protein expression levels of Th17-related ROR-γt,IL-17,IL-22 and IL-23 in the peripheral blood and reduced the number of Th9 cells and the m RNA and protein expression levels of Th9-related PU.1 and IL-9.CONCLUSION:XYJD granules were effective against PSV in patients with BHP by reducing the number of Th9 and Th17 cells and the levels of their related cytokines.展开更多
Graft-versus-host disease (GVHD) is a severe complication and a major source of morbidity and mortality after allogeneic hematopoietic stem cell transplantation (HSCT). Although T cell depletion of the allogeneic ...Graft-versus-host disease (GVHD) is a severe complication and a major source of morbidity and mortality after allogeneic hematopoietic stem cell transplantation (HSCT). Although T cell depletion of the allogeneic HSCT can efficiently prevent GVHD, it is associated with increased graft rejection and relapse of the malignant disease. To preserve the beneficial effects of donor T cells and avoid their GVHD effects, some approaches have been explored. One of them is to transfer a special suicide gene into the donor T lymphocytes so that they become more sensitive to a specific drug that is ordinarily not toxic. The most commonly used suicide gene is the thymidine kinase-encoding gene of herpes simplex virus (HSV-tk).展开更多
文摘Colon cancer is still one of the leading causes of cancer death worldwide. Although the host immune system has been shown to react against tumor cells, mainly through tumor infi ltrating lymphocytes and NK cells, tumor cells may utilize different ways to escape anti-tumor immune response. Tumor infi ltration of CD8+ and CD4+ (T-bet+) effector T cells has been attributed to a beneficial outcome, and the enhancement of T cell activation through T cell receptor stimulation and co-stimulatory signals provides promising strategies for immunotherapy of colon cancer. Growing evidence supports a role for the Fas/FasL system in tumor immunology, although the mechanisms and consequences of FasL activation in colon cancer are not completely understood. In animal models, depletion of regulatory T cells (CD4+ CD25+ T cells) can enhance the anti-tumor immune response under certain conditions. Taken together, recent insights in the immune reaction against colon carcinoma have provided new approaches to immunotherapy, although much remains to be learned about the exact mechanisms.
基金This study-was supported by the Traditional Chinese Medical Science Foundation of Zhejiang Province (No. 2005C052).
文摘Objective: To investigate the effect and clinical significance of Xuebijing injection on peripheral T-lymphocyte subpopulations in patients with severe trauma. Methods: Thirty-three patients with severe trauma were randomly divided into a control group (n=16) and a treatment group (n=17). The patients of two groups were all treated conventionally, and the only difference was that Xuebijing injection was given to patients of the treatment group. The CD4^+ and CD8^+ subpopulations of T-lymphocyte in the peripheral blood were detected respectively on admission, 3rd and 5th days after trauma by double antibody labeling and flow cytometry. Results: The CD4^+ T-lymphocytes and CD4^+/CD8^+ ratio of peripheral blood in patients with severe trauma decreased markedly on the 3rd and 5th days after trauma. Furthermore, compared with control group, the peripheral CD4^+ T-lymphocytes and CD4^+/CD8^+ ratio of treatment group renewed obviously on the 5th day after trauma, and showed statistical differences (P〈0.05). Conelusion: In the treatment of patients with severe trauma, the early use of Xuebijing injection is effective in correcting disorder or suppression of T-lymphocyte subpopulations regulating network, and promoting a more balanced profile of immunologic function.
文摘OBJECTIVE: To investigate the compositions of Th1/Th2/Th3 cells in chronic hepatitis B virus (HBV)-infected individuals by determining the expression of interleukin-4 (IL-4), inetrferon-gamma (IFN-gamma), and transform growth factor-beta (TGF-beta) in single CD4(+) T cells isolated from peripheral blood mononuclear cells (PBMCs) and the role of polarized Th cell populations in chronic HBV-infection was discussed. METHODS: PBMCs from chronically infected HBV individuals were isolated, stimulated by PMA/Ionomycin/Monensin, and IL-4, IFN-gamma and TGF-beta production by CD4(+) T cells was determined by using fluorescence activated cell sorter (FACS) analysis. RESULTS: The percentage of IFN-gamma-producing T cells, IL-4-producing T cells and TGF-beta-producing T cells ranged from 2.3% - 18.6%, 1.1% - 8.7% and 0.7% - 7.1% respectively in CD4(+) T cells from non-infected individuals. Most of CD4(+) T cells from PBMCs in chronically infected HBV individuals were Th0 cells. The proportion of Th1 cells increased significantly with hepatic inflammatory activity, and in the active period of chronic hepatitis B infection were higher than those in the non-active period (P 0.05), but were higher than that from controls (P
基金This work was supported by a grant from the Medical and Health Science Foundation of Zhejiang Province, China (No. 2009B052).
文摘Background Hemorrhagic shock induces immune dysfunction. Regulatory T cells (Tregs), T-helper (Th) cells, and cytotoxic T-lymphocytes (CTLs) can execute many crucial actions in immune and inflammatory responses. This study was conducted to investigate the early pathophysiological changes of CD4+CD25+Foxp3+ Treg and Th1/Th2, Tc1/Tc2 profiles in the peripheral blood of rats with controlled hemorrhagic shock and no fluid resuscitation. Methods A rat model of controlled hemorrhagic shock with no fluid resuscitation was established. Peripheral blood samples were taken before and four hours after hemorrhagic shock with no fluid resuscitation. Three color flow cytometry was used to detect Tregs, Thl, Th2, Tcl and Tc2 ceils in the samples. Results In the peripheral blood of rats, the percentage of Tregs four hours after hemorrhagic shock was significantly lower than before hemorrhagic shock (P=0.001). The ratios of Th1/Th2 and Tc1/Tc2 were changed from (23.08±8.98)% to (23.91±15.36)%, and from (40.40±21.56)% to (65.48±23.88)%, respectively. Conclusions At an early stage, the advent of hemorrhagic shock is related to an early decrease of Tregs, and a mild shift in the Th1/Th2, Tc1/Tc2 balance toward Thl and Tcl dominance. These changes are part of a hyper-inflammatory state of the host, and will deteriorate the maintenance of immune balance. Further influences and detailed mechanisms need to be investigated.
基金ThisresearchwassupportedbyagrantfromtheShannxiProvincialScienceFoundationofPublicHealthBureau (No .0 0 12 2 )
文摘OBJECTIVE: To establish a serum-free culture system of dendritic cells (DCs) from chronic myeloid leukemia (CML) cells so that DCs vaccine may be applied to the adoptive immunotherapy of CML in the near future. METHODS: Fetal calf serum, serum-free medium and autologous serum were used for culture of DCs. The usage of cytokines was classified into two groups: group A (stem cell factor, granulocyte/macrophage colony-stimulating-factor, tumor necrosis factor-alpha and interleukin-4) and group B (granulocyte/macrophage colony-stimulating-factor, tumor necrosis factor-alpha and interleukin-4). The phenotypes of DCs were analyzed by using indirect immunofluorescence and flow cytometry. Mixed leukocyte responses were performed by methyl thiazolyl tetrazolium (MTT) assay. Chromosome analysis of DCs can be achieved by displaying G banding. T cells from CML patients were stimulated with autologous DCs and T-cell cytotoxicity was measured by (MTT) assay. RESULTS: CD34(+) cells or mononuclear cells were obtained from peripheral blood or bone marrow samples of eight patients of chronic-phase CML. Group A of serum-free medium was better than group B in expansion of total cell numbers and the rate of DCs. These results of serum-free medium were not significantly different from those of fetal calf serum medium, but the results of autologous serum medium were inferior to two groups above. The expression of major histocompatibility complex class II antigen on the surface of DCs was notable (> 50%), but the expression of CD83 and the costimulatory molecules CD86 was not noticeable (10% - 50%). Although CD1a(+)/CD14(-) DCs were potent stimulators of allogeneic lymphocytes, expansion of T cells from normal volunteers were not significant (average 27.2 fold at DCs: T cells ratio of 1:10). At day 12, CD1a(+) cells from three patients were studied by displaying G banding and Ph(+) cells in these populations were 100%, 98% and 60%, respectively. At an effector: target ratio of 40:1, 32% to 45% cytotoxicity was noted with DC-stimulated T cells against autologous leukemia cells. CONCLUSIONS: A stable serum-free culture system of CML-DCs was established. The expression of CD83 and CD86 on the surface of CML-DCs and DCs' potent stimulation of allogeneic lymphocytes were not notable. DCs in CML patients can be derived from the malignant clone and these malignant DCs could induce anti-leukemic reactivity in autologous T lymphocytes without the necessity for additional exogenous antigens.
基金Supported by grants from the Chinese National Natural Science Foundation Effect and Action of Cooling Blood and Removing Toxins Traditional Chinese Medicine on New T Cells Subsets and Related Cytokines in Patients with Psoriasis Vulgaris(No.81403403)Immunological Mechanisms Research of Psoriasis Discuss of Traditional Chinese Medicine Based on Imbalance Theory of Helper T Cell(Th)1/Th2,Th17/Regulatory T Cells(Tregs)(No.81403404)+2 种基金The Study on the Relationship Between New T Helper Cells Subsets Th17,Th22,Effect Factor Interleukin(IL)-22 and Syndrome Differentiation Treatment of Psoriasis(No.81273755)2016 Beijing University of Chinese Medicine Foundation for Distinguished Young Scholars Study on The Mechanism of Cooling Blood Detoxification on Different Histopathological Levels of Psoriasis(No.2016-JYB-XJQ005)Young Scientist Development Program 2016,Dong Zhimen Hospital,Affiliated to Beijing University of Chinese Medicine(No.DZMYS-201603)
文摘OBJECTIVE:To evaluate the effectiveness of Xiaoyin Jiedu(XYJD)granules in the treatment of psoriasis vulgaris(PSV)in patients with a blood-heat pattern(BHP)in terms of Traditional Chinese Medicine(TCM).We also aimed to identify the possible underlying immunological mechanism.METHODS:Twenty-five PSV patients with BHP and ten normal controls were enrolled from January 1,2015 to December 31,2016.Patients were randomly assigned to either the XYJD group(15 cases)or the placebo group(10 cases),in which patients were treated with XYJD granules or a placebo,respectively.Additionally,albolene was used to relieve skin dryness in these two groups.The psoriasis area and severity indexes,dermatology life quality indexes and itching scores were assessed at the end of the 2 nd,4 th and 8 th week of treatment.The number of peripheral blood T helper(Th)9,Th17 and regulatory T cells(Tregs)and the m RNA and protein expression levels of PU.1,RAR-related orphan receptor(ROR)-γt,forkhead box protein 3(Foxp3),interleukin(IL)-9,IL-17,IL-23 and IL-10 in the control and experimental groups were compared before and after treatment.RESULTS:Psoriasis area and severity indexes and itching scores of patients in the XYJD group were significantly lower than those in the placebo group,whereas dermatology life quality indexes were significantly higher.In comparison with the placebo group,XYJD granules significantly reduced the number of Th17 cells and the m RNA and protein expression levels of Th17-related ROR-γt,IL-17,IL-22 and IL-23 in the peripheral blood and reduced the number of Th9 cells and the m RNA and protein expression levels of Th9-related PU.1 and IL-9.CONCLUSION:XYJD granules were effective against PSV in patients with BHP by reducing the number of Th9 and Th17 cells and the levels of their related cytokines.
文摘Graft-versus-host disease (GVHD) is a severe complication and a major source of morbidity and mortality after allogeneic hematopoietic stem cell transplantation (HSCT). Although T cell depletion of the allogeneic HSCT can efficiently prevent GVHD, it is associated with increased graft rejection and relapse of the malignant disease. To preserve the beneficial effects of donor T cells and avoid their GVHD effects, some approaches have been explored. One of them is to transfer a special suicide gene into the donor T lymphocytes so that they become more sensitive to a specific drug that is ordinarily not toxic. The most commonly used suicide gene is the thymidine kinase-encoding gene of herpes simplex virus (HSV-tk).