Thichosanthin(Tk), a polypeptide with 249 amino acid residues isolated and purified from a Chinese medicinal herb, showed the capability of inducing abortion and was able to inhibit tumor growth and HIV replication. O...Thichosanthin(Tk), a polypeptide with 249 amino acid residues isolated and purified from a Chinese medicinal herb, showed the capability of inducing abortion and was able to inhibit tumor growth and HIV replication. Owing to sequence homology of the peptide with a ribosomeinactivating protein, the downward activity of Tk was suggested to be related to its cytotoxic property. We report here, however, that Tk could exert potent inhibitory effects on human lymphoproliferative responses in vitro to allogeneic, mitogenic and soluble antigens with 50% inhibition doses ranged between 0.05 and 0.5 μg/ml. The lowresponsiveness caused by Tk was not due to toxic cytolysis. Rather, evidences suggested that, in the dose range adopted, the Tk-induced inhibition was attributable, at least in part, to immune suppression, in view of (1) Tk was more effective in the early stage of alloreactivity; (2)Suppression also occurred if responder cells were pulsetreated with Tk rather than cocultured; (3) Irradiated Tk-pulsed cells were capable of inducing suppression in a Tk-free culture; (4) Suppression could also be transferred by the supernatants of Tk-pulsed cultured cells; (5) Tkinduced immune suppression was diminished by depletion of CD8+ cells from the culture, and, finally; (6) Adding CD8+ cells back to the culture could restore the suppres Trichosanthin-induced humall immune suppression sion. Thus the possibility that Tk might function as a down-regulator by immunological mechanisms in human immune responses is discussed.展开更多
T cell immunoglobulin and mucin domain 3 (Tim-3) is well known to negatively regulate T cells responses, but its role in burn-induced T cells immune suppression remains unclear. In the present study, in order to ide...T cell immunoglobulin and mucin domain 3 (Tim-3) is well known to negatively regulate T cells responses, but its role in burn-induced T cells immune suppression remains unclear. In the present study, in order to identify the relationship between Tim-3 expression and post-burn T cells immune suppression, C57BL/6 mice were subjected to burn injury or sham injury, and the liver and spleen were harvested at the day 1 after operation. The expression level of Tim-3 on hepatic or splenic T cells and the functional properties of Tim-3+ T cells were evaluated. It was found burn injury induced dramatically elevated Tim-3 expression on both hepatic and splenic CD4+ and CD8+ T cells in contrast with the post-burn depletion of T cells. Furthermore, Tim-3 expression was correlated with the suppressive phenotype of T cells following burn injury, including increased expression of anti-inflammatory cytokine IL-10, decreased expression of pro-inflammatory cytokines IFN-γ and TNF-α, reduced T cell proliferation and elevated co-expression of Tim-3 and PD-1. Moreover, Tim-3+ T cells subsets were more prone to spontaneous apoptosis than Tim-3- T cells subsets. Our findings reinforce the idea that the up-regulated expression of Tim-3 on T cells after burn injury plays an important role in the development and maintenance of burn-induced T cell immune suppression.展开更多
Objective:To investigate the efficacy and immune function of thyroid stimulating hormone(TSH)suppression therapy in postoperative thyroid cancer patients.Methods:Sixty thyroid cancer patients admitted from July 2020–...Objective:To investigate the efficacy and immune function of thyroid stimulating hormone(TSH)suppression therapy in postoperative thyroid cancer patients.Methods:Sixty thyroid cancer patients admitted from July 2020–July 2022 were recruited and randomly divided into two groups.The control group(30 patients)received hormone replacement therapy,while the study group(30 patients)received TSH suppression therapy.The thyroid function,clinical efficacy,immune function,and tumor markers of the two groups were compared.Results:After treatment,the levels of free triiodothyronine(FT3)and thyroxine(FT4)in both groups increased significantly,while TSH levels decreased significantly.Moreover,the magnitude of change in the study group was greater than that in the control group(P<0.05).The total effective rate in the study group was significantly higher as compared to the control group(P<0.05).After treatment,the levels of CD3+and CD4+cells in both groups of patients increased significantly,with the study group showing significantly higher levels than the control group,whereas the level of CD8+cells decreased significantly,with the study group having lower levels than the control group(P<0.05).After treatment,the levels of Tg and CEA in both groups were significantly lowered as compared to before treatment,and the levels of Tg and CEA in the study group were significantly lower than the control group(P<0.05).Conclusion:TSH suppression therapy in postoperative thyroid cancer patients can improve thyroid function,suppress the levels of tumor markers,and enhance immune function,thereby achieving good clinical outcomes.展开更多
Ovarian cancer accounts for only 3% of all cancers in women, but it causes more deaths than any other gynecologic cancer. Treatment with chemotherapy and cytoreductive surgery shows a good response to the therapy. How...Ovarian cancer accounts for only 3% of all cancers in women, but it causes more deaths than any other gynecologic cancer. Treatment with chemotherapy and cytoreductive surgery shows a good response to the therapy. However, in a large proportion of the patients the tumor grows back within a few years. Cancer stem cells, that are less responsive to these treatments, are blamed for this recurrence of disease. Immune therapy either cellular or humoral is a novel concept to treat cancer. It is based on the notice that immune cells invade the tumor. However, the tumor invest heavily to escape from immune elimination by recruiting several immune suppressive mechanisms. These processes are normally in place to limit excessive immune activation and prevent autoimmune phenomena. Here, we discuss current knowledge about the immune(suppressive)status in ovarian cancer. Moreover, we discuss the immunological targets of ovarian cancer stem cells.展开更多
Fuzheng Jiedu granule exhibits a number of health benefits and it is thought that the mechanisms involved in these effects are due to the modulation of immunity. In this article, we studied the effect of Fuzheng Jiedu...Fuzheng Jiedu granule exhibits a number of health benefits and it is thought that the mechanisms involved in these effects are due to the modulation of immunity. In this article, we studied the effect of Fuzheng Jiedu granule on immunological function and the expression of immune-related cytokines in immune-suppressed mice. 72 mice were randomly divided into six groups, with 12 in each group. The control groups included an untreated group, a negative control group(Cyclophosphamide) and a positive control group(Astragalus polysaccharide). There were three treated groups, which were given different doses of Fuzheng Jiedu granule: a low dose(100 mg kg^(–1)), a medium dose(400 mg kg^(–1)) and a high dose(600 mg kg^(–1)). With the exception of the untreated control animals, each group received an intraperitoneal injection of Cyclophosphamide(100 mg kg^(–1)) for 3 days to establish the immune-suppressed model. Mice were then treated for 19 consecutive days and, 24 h after the last treatment, blood was taken for the eyeballs and serum separation was performed. Analysis was made of the levels of related cytokines(IgA, IgG, IgM, IL-6, IFN-γ, C3, C4 and TNF-α), the transformation of lymphocytes and the immune organ indexes. The results showed that Fuzheng Jiedu granule can improve the levels of cytokines, the rate of proliferation of lymphocytes and the immune organ indexes of immune-suppressed mice.展开更多
Prostate cancers(PCa)have been reported to actively suppress antitumor immune responses by creating an immune-suppressive microenvironment.There is mounting evidence that PCas may undergo an‘‘Epithelial Immune Cell-...Prostate cancers(PCa)have been reported to actively suppress antitumor immune responses by creating an immune-suppressive microenvironment.There is mounting evidence that PCas may undergo an‘‘Epithelial Immune Cell-like Transition’’(EIT)by expressing molecules conventionally associated with immune cells(e.g.,a variety of cytokines/receptors,immune transcription factors,Ig motifs,and immune checkpoint molecules),which subsequently results in the suppression of anti-cancer immune activity within the tumor microenvironment.Recent progress within the field of immune therapy has underscored the importance of immune checkpoint molecules in cancer development,thus leading to the development of novel immunotherapeutic approaches.Here,we review the expression of select immune checkpoint molecules in PCa epithelial and associated immune cells,with particular emphasis on clinical data supporting the concept of an EIT-mediated phenotype in PCa.Furthermore,we summarize current advances in anti-immune checkpoint therapies,and provide perspectives on their potential applicability.展开更多
Steroids continue to be the cornerstone of immune suppression since the early days of organ transplantation.Steroids are key component of induction protocols,maintenance therapy and in the treatment of various forms o...Steroids continue to be the cornerstone of immune suppression since the early days of organ transplantation.Steroids are key component of induction protocols,maintenance therapy and in the treatment of various forms of rejection.Prolonged steroid use resulted in significant side effects on almost all the body organs owing to the presence of steroid receptors in most of the mammalian cells.Kidney allograft recipients had to accept the short and long term complications of steroids because of lack of effective alternatives.This situation changed with the introduction of newer and more effective immune suppression agents with a relatively more acceptable side effect profile.As a result,the clinicians have been contemplating if it is the time to abandon the unquestionable reliance on maintenance steroids in modern transplantation practice.This review aims to evaluate the safety and efficacy of various steroid-minimization approaches(steroid avoidance,early steroid withdrawal,and late steroid withdrawal)in kidney transplant recipients.A meticulous electronic search was conducted through the available data resources like SCOPUS,MEDLINE,and Liverpool University library e-resources.Relevant articles obtained through our search were included.A total number of 90 articles were eligible to be included in this review[34 randomised controlled trials(RCT)and 56 articles of other research modalities].All articles were evaluating the safety and efficacy of various steroidfree approaches in comparison to maintenance steroids.We will cover only the RCT articles in this review.If used in right clinical context,steroid-free protocols proved to be comparable to steroid-based maintenance therapy.The appropriate approach should be tailored individually according to each recipient immunological challenges and clinical condition.展开更多
Objective:To investigate the effects of Bortezomib and Dexamethasone combination on treating senile multiple myeloma and influence on immune suppressed factors and immune cell levels.Methods:A total of 80 cases of pat...Objective:To investigate the effects of Bortezomib and Dexamethasone combination on treating senile multiple myeloma and influence on immune suppressed factors and immune cell levels.Methods:A total of 80 cases of patients with multiple myeloma treated in our hospital from Oct 2013 to Jul 2015 were selected as investigate subjects. They were randomly divided to be observation group consisted of 43 cases and control group consisted of 37 cases. For observation group, treatment of Bortezomib and Dexamethasone combination was provided. For control group, Vincristine + Epirubicin + Dexamethasone treatment was provided. After three courses, effects on two groups of patients were compared, and immune suppressed factors and immune cell levels before and after treatment in different periods were compared.Results:After three courses of treatment, the total effective rate in observation group was significantly higher than control group. Before treatment, IL-6, IL-17, TGF-β, CD3+CD4+, CD3+CD8+ and CD3+CD4+/CD3+CD8+ between the two group of patients were compared, no significant difference showed;After treatment for 6 weeks, IL-6, IL-17 levels in observation group were significantly decreased comparing with the same group before treatment;After treatment for 12 weeks, IL-6, IL-17 and TGF-β levels in observation group were significantly decreased comparing with the same group before treatment;After treatment, IL-6, IL-17 levels in observation group were significantly lower than control group at the same phase. After treatment for 12 weeks, CD3+CD4+, CD3+CD4+/CD3+CD8+ in observation group were significantly higher than the same group before treatment, and significantly higher than control group at the same phase;CD3+CD8+ in observation group was significantly lower than the same group before treatment, and significantly lower than control group at the same phase. Conclusion:Compared with Vincristine + Epirubicin + Dexamethasone treatment, Bortezomib and Dexamethasone combination on treating senile multiple myeloma had more significant effects, which deserves further clinical researches.展开更多
We have reported a new innate-like CD4 T cell population that expresses cell surface makers of effector/memory cells and produce Th1 and Th2 cytokines immediately upon activation. Unlike conventional CD4 T cells that ...We have reported a new innate-like CD4 T cell population that expresses cell surface makers of effector/memory cells and produce Th1 and Th2 cytokines immediately upon activation. Unlike conventional CD4 T cells that are selected by thymic epithelial cells, these CD4 T cells, named T-CD4 T cells, are selected by MHC class II expressing thymocytes. Previously, we showed that the presence of T-CD4 T cells protected mice from airway inflammation suggesting an immune regulatory role of T-CD4 T cells. To further understand the function of T-CD4 T cells, we investigated immune responses mediated by T-CD4 T cells during bacterial infection because the generation of antigen specific CD4 T cells contributes to clearance of infection and for the development of immune memory. The current study shows a suppressive effect of T-CD4 T cells on both CD8 and CD4 T cell-mediated immune responses during Listeria and Helicobacter infections. In the mouse model of Listeria monocytogenes infection, T-CD4 T cells resulted in decreasedfrequency of Listeria-specific CD8 T cells and the killing activity of them. Furthermore, mice with T-CD4 T cells developed poor immune memory, demonstrated by reduced expansion of antigen-specific T cells and high bacterial burden upon re-infection. Similarly, the presence of T-CD4 T cells suppressed the generation of antigen-specific CD4 T cells in Helicobacter pylori infected mice. Thus, our studies reveal a novel function of T-CD4 T cells in sup-pressing anti-bacterial immunity.展开更多
<em>L. donovani</em> infections (visceral and post kala-azar dermal leishmaniases) are characterized by infection-induced reversible immune suppression. Autoimmunity is a well-documented phenomenon among p...<em>L. donovani</em> infections (visceral and post kala-azar dermal leishmaniases) are characterized by infection-induced reversible immune suppression. Autoimmunity is a well-documented phenomenon among patients with primary immune deficiencies. This study aimed to study auto-immune phenomena accompanying <em>L. donovani</em> infections. In a prospective case-controlled study and following informed consent, 155 individuals with visceral leishmaniasis (VL;<em>n</em> = 62), post kala-azar dermal leishmaniasis (PKDL;<em>n</em> = 31) and apparently healthy volunteers (<em>n</em> = 62) were recruited. Sera antinuclear (ANA), anti-dsDNA, anti-thyroid peroxidase (TPO), anti-smooth muscles (ASMA) and F-actin auto-antibodies were measured using ELISA and indirect immune-fluorescence assay. The mean ages of VL, PDKL patients and apparently healthy volunteers were: 17.5 ± 12.5, 15.0 ± 7.0 and 17.5 ± 9.5 years with Male:Female ratios of 2:0, 1:2 and 1:5 respectively. Significantly high frequencies of F-actin (74.2%;46/62) and ASMA (50%;31/62) auto-antibodies were seen among VL patients (<strong><em>p</em> = 0.003</strong>, <strong><em>p</em> = 0.001</strong>) compared to apparently healthy volunteers. Likewise, significantly high frequencies of F-actin (64.5%;20/31;<strong><em>p</em> = 0.001</strong>), ASMA (42%;13/31;<strong><em>p</em> = 0.003</strong>), ANA (36%;11/31;<strong><em>p</em> = 0.00</strong><strong>1</strong>) and anti-dsDNA (16%;5/31;<strong><em>p</em> = 0.01</strong>) auto-antibodies were seen among PKDL patients. Development of tissue-based autoantibodies in <em>L. donovani</em> infections probably indicates loss of peripheral tolerance with activation of circulating auto-reactive T and B cells probably contributing to disease pathogenesis (increased bilirubin/liver enzymes, prolonged QT interval/arrythmias and blood cytopenias). In conclusion, <em>L. donovani</em> infection-induced immune suppression with development of tissue-based auto-antibodies is prevalent among Sudanese patients with VL and PKDL leishmaniases and contributes to some aspects of the disease pathogenesis.展开更多
Despite the initial successes of the Bacillus Calmette-Guerin(BCG)vaccine in children,its efficacy against tuberculosis is highly variable.There is a lack of understanding about how mental conditions influence BCG vac...Despite the initial successes of the Bacillus Calmette-Guerin(BCG)vaccine in children,its efficacy against tuberculosis is highly variable.There is a lack of understanding about how mental conditions influence BCG vaccination.Here,we used the chronic social defeat stress(CSDS)model to explore the effects of depression on BCG vaccination efficacy.We observed higher lung and spleen bacterial loads and a lower organ index in depressed compared to BCG mice.Meanwhile,a relatively lower T cell protective efficacy was observed in both compared to control and BCG mice via a mycobacterium growth inhibition assay(MGIA).Cytokine expression of IL-12p40,IL-1β,IL-17,TNF-αand IFN-γwas reduced,whereas the expression of IL-10 and IL-5 was increased in the spleen of both compared to BCG mice.Moreover,the proportions of CD4^(+)IFN-γ^(+),CD8^(+)IFN-γ^(+)T lymphocytes and CD4^(+)effector/central memory T cells were reduced in the splenocytes of the depressed BCG mice.Depression promotes CD4^(+)regulatory T cells(Treg)and myeloid-derived suppressor cell(MDSC)generation in depressed mice,contributing to the reduced pro-inflammatory immune response upon BCG vaccination.This study provides insight into the decreased protective immunity by BCG vaccination attributable to depression in mice.展开更多
文摘Thichosanthin(Tk), a polypeptide with 249 amino acid residues isolated and purified from a Chinese medicinal herb, showed the capability of inducing abortion and was able to inhibit tumor growth and HIV replication. Owing to sequence homology of the peptide with a ribosomeinactivating protein, the downward activity of Tk was suggested to be related to its cytotoxic property. We report here, however, that Tk could exert potent inhibitory effects on human lymphoproliferative responses in vitro to allogeneic, mitogenic and soluble antigens with 50% inhibition doses ranged between 0.05 and 0.5 μg/ml. The lowresponsiveness caused by Tk was not due to toxic cytolysis. Rather, evidences suggested that, in the dose range adopted, the Tk-induced inhibition was attributable, at least in part, to immune suppression, in view of (1) Tk was more effective in the early stage of alloreactivity; (2)Suppression also occurred if responder cells were pulsetreated with Tk rather than cocultured; (3) Irradiated Tk-pulsed cells were capable of inducing suppression in a Tk-free culture; (4) Suppression could also be transferred by the supernatants of Tk-pulsed cultured cells; (5) Tkinduced immune suppression was diminished by depletion of CD8+ cells from the culture, and, finally; (6) Adding CD8+ cells back to the culture could restore the suppres Trichosanthin-induced humall immune suppression sion. Thus the possibility that Tk might function as a down-regulator by immunological mechanisms in human immune responses is discussed.
基金supported by grants from National Natural Science Foundation of China (No. 30700799, 81172803)Doctoral Fund of Ministry of Education of China (No. 20070487119)Natural Science Foundation of Hubei Province (No. 2007AD A201)
文摘T cell immunoglobulin and mucin domain 3 (Tim-3) is well known to negatively regulate T cells responses, but its role in burn-induced T cells immune suppression remains unclear. In the present study, in order to identify the relationship between Tim-3 expression and post-burn T cells immune suppression, C57BL/6 mice were subjected to burn injury or sham injury, and the liver and spleen were harvested at the day 1 after operation. The expression level of Tim-3 on hepatic or splenic T cells and the functional properties of Tim-3+ T cells were evaluated. It was found burn injury induced dramatically elevated Tim-3 expression on both hepatic and splenic CD4+ and CD8+ T cells in contrast with the post-burn depletion of T cells. Furthermore, Tim-3 expression was correlated with the suppressive phenotype of T cells following burn injury, including increased expression of anti-inflammatory cytokine IL-10, decreased expression of pro-inflammatory cytokines IFN-γ and TNF-α, reduced T cell proliferation and elevated co-expression of Tim-3 and PD-1. Moreover, Tim-3+ T cells subsets were more prone to spontaneous apoptosis than Tim-3- T cells subsets. Our findings reinforce the idea that the up-regulated expression of Tim-3 on T cells after burn injury plays an important role in the development and maintenance of burn-induced T cell immune suppression.
文摘Objective:To investigate the efficacy and immune function of thyroid stimulating hormone(TSH)suppression therapy in postoperative thyroid cancer patients.Methods:Sixty thyroid cancer patients admitted from July 2020–July 2022 were recruited and randomly divided into two groups.The control group(30 patients)received hormone replacement therapy,while the study group(30 patients)received TSH suppression therapy.The thyroid function,clinical efficacy,immune function,and tumor markers of the two groups were compared.Results:After treatment,the levels of free triiodothyronine(FT3)and thyroxine(FT4)in both groups increased significantly,while TSH levels decreased significantly.Moreover,the magnitude of change in the study group was greater than that in the control group(P<0.05).The total effective rate in the study group was significantly higher as compared to the control group(P<0.05).After treatment,the levels of CD3+and CD4+cells in both groups of patients increased significantly,with the study group showing significantly higher levels than the control group,whereas the level of CD8+cells decreased significantly,with the study group having lower levels than the control group(P<0.05).After treatment,the levels of Tg and CEA in both groups were significantly lowered as compared to before treatment,and the levels of Tg and CEA in the study group were significantly lower than the control group(P<0.05).Conclusion:TSH suppression therapy in postoperative thyroid cancer patients can improve thyroid function,suppress the levels of tumor markers,and enhance immune function,thereby achieving good clinical outcomes.
基金Supported by The Dutch government to the Netherlands Institute for Regenerative Medicine,No.FES0908
文摘Ovarian cancer accounts for only 3% of all cancers in women, but it causes more deaths than any other gynecologic cancer. Treatment with chemotherapy and cytoreductive surgery shows a good response to the therapy. However, in a large proportion of the patients the tumor grows back within a few years. Cancer stem cells, that are less responsive to these treatments, are blamed for this recurrence of disease. Immune therapy either cellular or humoral is a novel concept to treat cancer. It is based on the notice that immune cells invade the tumor. However, the tumor invest heavily to escape from immune elimination by recruiting several immune suppressive mechanisms. These processes are normally in place to limit excessive immune activation and prevent autoimmune phenomena. Here, we discuss current knowledge about the immune(suppressive)status in ovarian cancer. Moreover, we discuss the immunological targets of ovarian cancer stem cells.
文摘Fuzheng Jiedu granule exhibits a number of health benefits and it is thought that the mechanisms involved in these effects are due to the modulation of immunity. In this article, we studied the effect of Fuzheng Jiedu granule on immunological function and the expression of immune-related cytokines in immune-suppressed mice. 72 mice were randomly divided into six groups, with 12 in each group. The control groups included an untreated group, a negative control group(Cyclophosphamide) and a positive control group(Astragalus polysaccharide). There were three treated groups, which were given different doses of Fuzheng Jiedu granule: a low dose(100 mg kg^(–1)), a medium dose(400 mg kg^(–1)) and a high dose(600 mg kg^(–1)). With the exception of the untreated control animals, each group received an intraperitoneal injection of Cyclophosphamide(100 mg kg^(–1)) for 3 days to establish the immune-suppressed model. Mice were then treated for 19 consecutive days and, 24 h after the last treatment, blood was taken for the eyeballs and serum separation was performed. Analysis was made of the levels of related cytokines(IgA, IgG, IgM, IL-6, IFN-γ, C3, C4 and TNF-α), the transformation of lymphocytes and the immune organ indexes. The results showed that Fuzheng Jiedu granule can improve the levels of cytokines, the rate of proliferation of lymphocytes and the immune organ indexes of immune-suppressed mice.
文摘Prostate cancers(PCa)have been reported to actively suppress antitumor immune responses by creating an immune-suppressive microenvironment.There is mounting evidence that PCas may undergo an‘‘Epithelial Immune Cell-like Transition’’(EIT)by expressing molecules conventionally associated with immune cells(e.g.,a variety of cytokines/receptors,immune transcription factors,Ig motifs,and immune checkpoint molecules),which subsequently results in the suppression of anti-cancer immune activity within the tumor microenvironment.Recent progress within the field of immune therapy has underscored the importance of immune checkpoint molecules in cancer development,thus leading to the development of novel immunotherapeutic approaches.Here,we review the expression of select immune checkpoint molecules in PCa epithelial and associated immune cells,with particular emphasis on clinical data supporting the concept of an EIT-mediated phenotype in PCa.Furthermore,we summarize current advances in anti-immune checkpoint therapies,and provide perspectives on their potential applicability.
文摘Steroids continue to be the cornerstone of immune suppression since the early days of organ transplantation.Steroids are key component of induction protocols,maintenance therapy and in the treatment of various forms of rejection.Prolonged steroid use resulted in significant side effects on almost all the body organs owing to the presence of steroid receptors in most of the mammalian cells.Kidney allograft recipients had to accept the short and long term complications of steroids because of lack of effective alternatives.This situation changed with the introduction of newer and more effective immune suppression agents with a relatively more acceptable side effect profile.As a result,the clinicians have been contemplating if it is the time to abandon the unquestionable reliance on maintenance steroids in modern transplantation practice.This review aims to evaluate the safety and efficacy of various steroid-minimization approaches(steroid avoidance,early steroid withdrawal,and late steroid withdrawal)in kidney transplant recipients.A meticulous electronic search was conducted through the available data resources like SCOPUS,MEDLINE,and Liverpool University library e-resources.Relevant articles obtained through our search were included.A total number of 90 articles were eligible to be included in this review[34 randomised controlled trials(RCT)and 56 articles of other research modalities].All articles were evaluating the safety and efficacy of various steroidfree approaches in comparison to maintenance steroids.We will cover only the RCT articles in this review.If used in right clinical context,steroid-free protocols proved to be comparable to steroid-based maintenance therapy.The appropriate approach should be tailored individually according to each recipient immunological challenges and clinical condition.
文摘Objective:To investigate the effects of Bortezomib and Dexamethasone combination on treating senile multiple myeloma and influence on immune suppressed factors and immune cell levels.Methods:A total of 80 cases of patients with multiple myeloma treated in our hospital from Oct 2013 to Jul 2015 were selected as investigate subjects. They were randomly divided to be observation group consisted of 43 cases and control group consisted of 37 cases. For observation group, treatment of Bortezomib and Dexamethasone combination was provided. For control group, Vincristine + Epirubicin + Dexamethasone treatment was provided. After three courses, effects on two groups of patients were compared, and immune suppressed factors and immune cell levels before and after treatment in different periods were compared.Results:After three courses of treatment, the total effective rate in observation group was significantly higher than control group. Before treatment, IL-6, IL-17, TGF-β, CD3+CD4+, CD3+CD8+ and CD3+CD4+/CD3+CD8+ between the two group of patients were compared, no significant difference showed;After treatment for 6 weeks, IL-6, IL-17 levels in observation group were significantly decreased comparing with the same group before treatment;After treatment for 12 weeks, IL-6, IL-17 and TGF-β levels in observation group were significantly decreased comparing with the same group before treatment;After treatment, IL-6, IL-17 levels in observation group were significantly lower than control group at the same phase. After treatment for 12 weeks, CD3+CD4+, CD3+CD4+/CD3+CD8+ in observation group were significantly higher than the same group before treatment, and significantly higher than control group at the same phase;CD3+CD8+ in observation group was significantly lower than the same group before treatment, and significantly lower than control group at the same phase. Conclusion:Compared with Vincristine + Epirubicin + Dexamethasone treatment, Bortezomib and Dexamethasone combination on treating senile multiple myeloma had more significant effects, which deserves further clinical researches.
文摘We have reported a new innate-like CD4 T cell population that expresses cell surface makers of effector/memory cells and produce Th1 and Th2 cytokines immediately upon activation. Unlike conventional CD4 T cells that are selected by thymic epithelial cells, these CD4 T cells, named T-CD4 T cells, are selected by MHC class II expressing thymocytes. Previously, we showed that the presence of T-CD4 T cells protected mice from airway inflammation suggesting an immune regulatory role of T-CD4 T cells. To further understand the function of T-CD4 T cells, we investigated immune responses mediated by T-CD4 T cells during bacterial infection because the generation of antigen specific CD4 T cells contributes to clearance of infection and for the development of immune memory. The current study shows a suppressive effect of T-CD4 T cells on both CD8 and CD4 T cell-mediated immune responses during Listeria and Helicobacter infections. In the mouse model of Listeria monocytogenes infection, T-CD4 T cells resulted in decreasedfrequency of Listeria-specific CD8 T cells and the killing activity of them. Furthermore, mice with T-CD4 T cells developed poor immune memory, demonstrated by reduced expansion of antigen-specific T cells and high bacterial burden upon re-infection. Similarly, the presence of T-CD4 T cells suppressed the generation of antigen-specific CD4 T cells in Helicobacter pylori infected mice. Thus, our studies reveal a novel function of T-CD4 T cells in sup-pressing anti-bacterial immunity.
文摘<em>L. donovani</em> infections (visceral and post kala-azar dermal leishmaniases) are characterized by infection-induced reversible immune suppression. Autoimmunity is a well-documented phenomenon among patients with primary immune deficiencies. This study aimed to study auto-immune phenomena accompanying <em>L. donovani</em> infections. In a prospective case-controlled study and following informed consent, 155 individuals with visceral leishmaniasis (VL;<em>n</em> = 62), post kala-azar dermal leishmaniasis (PKDL;<em>n</em> = 31) and apparently healthy volunteers (<em>n</em> = 62) were recruited. Sera antinuclear (ANA), anti-dsDNA, anti-thyroid peroxidase (TPO), anti-smooth muscles (ASMA) and F-actin auto-antibodies were measured using ELISA and indirect immune-fluorescence assay. The mean ages of VL, PDKL patients and apparently healthy volunteers were: 17.5 ± 12.5, 15.0 ± 7.0 and 17.5 ± 9.5 years with Male:Female ratios of 2:0, 1:2 and 1:5 respectively. Significantly high frequencies of F-actin (74.2%;46/62) and ASMA (50%;31/62) auto-antibodies were seen among VL patients (<strong><em>p</em> = 0.003</strong>, <strong><em>p</em> = 0.001</strong>) compared to apparently healthy volunteers. Likewise, significantly high frequencies of F-actin (64.5%;20/31;<strong><em>p</em> = 0.001</strong>), ASMA (42%;13/31;<strong><em>p</em> = 0.003</strong>), ANA (36%;11/31;<strong><em>p</em> = 0.00</strong><strong>1</strong>) and anti-dsDNA (16%;5/31;<strong><em>p</em> = 0.01</strong>) auto-antibodies were seen among PKDL patients. Development of tissue-based autoantibodies in <em>L. donovani</em> infections probably indicates loss of peripheral tolerance with activation of circulating auto-reactive T and B cells probably contributing to disease pathogenesis (increased bilirubin/liver enzymes, prolonged QT interval/arrythmias and blood cytopenias). In conclusion, <em>L. donovani</em> infection-induced immune suppression with development of tissue-based auto-antibodies is prevalent among Sudanese patients with VL and PKDL leishmaniases and contributes to some aspects of the disease pathogenesis.
基金funded by the National Natural Science Foundation of China(Grant No.U21A20259,31602061,31872470)the National Key Research and Development Program of China(Grant No.2021YFD1800401).
文摘Despite the initial successes of the Bacillus Calmette-Guerin(BCG)vaccine in children,its efficacy against tuberculosis is highly variable.There is a lack of understanding about how mental conditions influence BCG vaccination.Here,we used the chronic social defeat stress(CSDS)model to explore the effects of depression on BCG vaccination efficacy.We observed higher lung and spleen bacterial loads and a lower organ index in depressed compared to BCG mice.Meanwhile,a relatively lower T cell protective efficacy was observed in both compared to control and BCG mice via a mycobacterium growth inhibition assay(MGIA).Cytokine expression of IL-12p40,IL-1β,IL-17,TNF-αand IFN-γwas reduced,whereas the expression of IL-10 and IL-5 was increased in the spleen of both compared to BCG mice.Moreover,the proportions of CD4^(+)IFN-γ^(+),CD8^(+)IFN-γ^(+)T lymphocytes and CD4^(+)effector/central memory T cells were reduced in the splenocytes of the depressed BCG mice.Depression promotes CD4^(+)regulatory T cells(Treg)and myeloid-derived suppressor cell(MDSC)generation in depressed mice,contributing to the reduced pro-inflammatory immune response upon BCG vaccination.This study provides insight into the decreased protective immunity by BCG vaccination attributable to depression in mice.