Melatonin plays a critical role in regulating photoperiodic signals and has recently been shown to decrease immunosenescence with age. In this study, we examined whether melatonin activates T lymphocytes as major adap...Melatonin plays a critical role in regulating photoperiodic signals and has recently been shown to decrease immunosenescence with age. In this study, we examined whether melatonin activates T lymphocytes as major adaptive immune cells in in vitro and in vivo models. Splenocytes, CD4＋, and naive CD4 T lymphocytes were isolated from the spleen of BALB/c mice and the cell population patterns and mRNA profiles associated with T cell activation （CD28 and p21） and the melatonin receptor （MT1A and MT1B） were assessed. The T cell activation- related proteins Ki67 and Bcl2 were also evaluated to confirm the relationship between gene and protein levels. Our data clearly revealed that CD28, p21, MT 1 A, and MT 1B mRNA were highly expressed in the presence of melatonin. Co-culture of CD4＋ T lymphocyte and peritoneal macrophage 7 days after melatonin administration to young and aged mice significantly increased APRIL mRNA, suggesting induction or maintenance of T lymphocyte responses. We also found that the intracellular amount of Ki67 and Bcl2 proteins were significantly upregulated in aged CD4＋ T lymphocytes, suggesting enhancing T cell proliferation and ling-term maintenance of memory T cells. Taken together, we conclude that melatonin supplementation may enhance immunity in aged individuals by upregulating immunosenescence indices in association with T lymphocytes and may be an attractive pharmacological candidate for aged and immunocompromised individuals.展开更多
目的探讨中药复方提取物湘A-1（Hu Nan A-1,HNA-1）对猴免疫缺陷病毒（Simian immunodeficiency virus,SIV）慢性感染中国恒河猴胸腺输出功能的影响。方法采用SIVmac239病毒液对8只中国恒河猴进行感染16~21个月,随机分为对照组和治疗组...目的探讨中药复方提取物湘A-1（Hu Nan A-1,HNA-1）对猴免疫缺陷病毒（Simian immunodeficiency virus,SIV）慢性感染中国恒河猴胸腺输出功能的影响。方法采用SIVmac239病毒液对8只中国恒河猴进行感染16~21个月,随机分为对照组和治疗组,每组4只。治疗组给予HNA-1灌胃20 m L治疗,每日1次;对照组给予等体积生理盐水灌胃。两组给药2个月。观察两组一般情况、体重,采用实时荧光定量PCR方法检测两组血浆病毒载量,采用流式细胞法检测CD4比例及数量、CD4的初始亚群,实时荧光定量PCR法检测T细胞受体DNA重排删除环（TREC）,常规HE染色后观察胸腺组织的病理情况。分析胸腺组织病变情况与CD4细胞数、初始型CD4细胞数及TREC的关联性。结果治疗后两组体重、病毒载量、CD4比例绝对数比较,差异无统计学意义（P〉0.05）。对照组TREC改变倍数明显呈下降趋势,治疗组总体呈明显的上升趋势,两组间差异有统计学意义（P〈0.05）。两组动物的胸腺组织均可见结构破坏、粉红色无结构样物质填充、结缔组织增多、细胞密度降低、排列紊乱等病理改变,未见明显区别。TREC含量与初始型CD4去除极值后,呈正相关（r=0.926,P=0.001）;而初始型CD4数量与CD4数量呈正相关（r=0.961,P=0.005）。结论检测TREC含量来测定新胸腺迁出细胞数量可作为评价胸腺输出功能的检测方法,且HNA-1可增加胸腺的输出功能,而TREC、初始型CD4数量及胸腺组织病理情况之间存在一定相关关系,在感染晚期尤为明显。展开更多
Objective: To evaluate the virological status of ineligible HIV patients for anti-retroviral therapy based on the criterion of CD4+ T lymphocytes rate over than 350/μl of blood. Method: This is a prospective study wh...Objective: To evaluate the virological status of ineligible HIV patients for anti-retroviral therapy based on the criterion of CD4+ T lymphocytes rate over than 350/μl of blood. Method: This is a prospective study which was conducted from November 2011 to July 2012 in the tropical and infectious disease department of CHU Sylvanus Olympio of Lomé. All HIV-1 infected patients whose CD4+ T lymphocytes rate was ≥350/μl of blood were retained. The count of CD4+ T lymphocytes was made by cytometer FACSCalibur? flow of BD biosciences and the determination of viral load was achieved by NASBA laboratory method of Biomérieux. Results: We have recruited 102 PLWHA aged between 19 and 58 years with a median of 35 years. Biologically, 102 patients had a T-CD4 rate between 355 and 432/μl of blood. The determination of viral load showed a very high viral replication more than 10,000 copies/ml among all patients and 28 (27.5%) patients had a viral load > 100,000 copies/ml of blood. Conclusion: Our results argue for a reconsideration of the criteria for starting antiretroviral therapy in Togo by including virological data if necessary in patients with T-CD4 rate below 500/μl of blood.展开更多
Objective To establish a stable and efficient method of culturing imDCs in vitro,and to explore the effect of GW5074,which blocks ERK1 /2 signal pathway in the process of immature dentritic cells ( imDCs) on inducing ...Objective To establish a stable and efficient method of culturing imDCs in vitro,and to explore the effect of GW5074,which blocks ERK1 /2 signal pathway in the process of immature dentritic cells ( imDCs) on inducing differentiation of the naive allogeneic CD4 + T展开更多
Background: Hepcidin is the principal regulator of iron absorption and its tissue distribution. Its correlation with iron homeostasis in individuals infected with human immunodeficiency virus type-1 (HIV-1) treated wi...Background: Hepcidin is the principal regulator of iron absorption and its tissue distribution. Its correlation with iron homeostasis in individuals infected with human immunodeficiency virus type-1 (HIV-1) treated with different regimens of highly active antiretroviral therapy (HAART) was investigated. Methods: Serum hepcidin levels were determined in 448 volunteers. Of these, 372 were HIV-1-infected individuals, and 93 did not receive HAART (ART-naïve) while 279 received HAART consisting of a non-nucleoside reverse transcriptase inhibitor (NNRTI-based) and protease inhibitors (PI-based);both were used in association with a nucleoside reverse transcriptase inhibitor (NRTI). Seventy-six additional HIV-1 seronegative individuals were enrolled in the study. The following parameters were quantified: hematological parameters, iron biomarkers and markers of infection (CD4+ and CD8+ T-cells), and HIV-1 RNA (viral load). Results: Serum hepcidin, iron and ferritin levels, as well as the marker of infection, CD4+ T-cells, were significantly lower in the ART-naïve group compared with other groups. Additionally, transferrin saturation, iron binding capacity, hemoglobin level and erythrocyte level were not significantly different, and anemia was not observed in the different groups. Conclusions: HIV-1 infection affected serum hepcidin, iron and ferritin levels in the ART-naïve group, and the different HAART regimens restored the levels of hepcidin and iron homeostasis in HIV-1-infected individuals who have undetectable HIV-1 RNA levels.展开更多
Background：Among HlV-infected patients initiating antiretroviral therapy （ART）,early changes in CD4＋ T-cell subsets are well described.However,HIV-infected late presenters initiating treatment present with a subop...Background：Among HlV-infected patients initiating antiretroviral therapy （ART）,early changes in CD4＋ T-cell subsets are well described.However,HIV-infected late presenters initiating treatment present with a suboptimal CD4＋ T-cell reconstitution and remain at a higher risk for AIDS and non-AIDS events.Therefore,factors associated with CD4＋ T-cell reconstitution need to be determined in this population,which will allow designing effective immunotherapeutic strategies.Methods：Thirty-one adult patients with baseline CD4＋ T-cell count 〈350 cells/mm^3 exhibiting viral suppression after ART initiation were followed in the HIV/AIDS research center of Peking Union Medical College Hospital in Beijing,China,from October 2002 to September 2013.Changes in T-cell subsets and associated determinants were measured.Results：Median baseline CD4＋ T-cell count was 70 cells/mm3.We found a biphasic reconstitution ofT-cell subsets and immune activation：a rapid change during the first 6 months followed by a more gradual change over the subsequent 8 years.Baseline CD4＋ T-cell count 〉200 cells/ mm3 in comparison to CD4＋ T-cell count ≤200 cells/mm3 was associated with more complete immune Reconstitution （77.8% vs.27.3% respectively;P =0.017） and normalized CD4/CD8 ratio.We showed that the baseline percentage of naive CD4＋ T-cell was a predictive marker for complete immune reconstitution （area under receiver operating characteristic curve 0.907）,and 12.4% as cutoffvalue had a sensitivity of 84.6% and a specificity of 88.2%.Conclusions：Baseline naive CD4＋ T-cell percentage may serve as a predictive marker for optimal immune reconstitution during long-term therapy.Such study findings suggest that increasing thymic output should represent an avenue to improve patients who are diagnosed late in the course of infection.展开更多
基金supported by High Value-added Food Technology Development Program,Ministry of Agriculture,Food and Rural Affairs(MAFRAgrant number 113034-3)
文摘Melatonin plays a critical role in regulating photoperiodic signals and has recently been shown to decrease immunosenescence with age. In this study, we examined whether melatonin activates T lymphocytes as major adaptive immune cells in in vitro and in vivo models. Splenocytes, CD4＋, and naive CD4 T lymphocytes were isolated from the spleen of BALB/c mice and the cell population patterns and mRNA profiles associated with T cell activation （CD28 and p21） and the melatonin receptor （MT1A and MT1B） were assessed. The T cell activation- related proteins Ki67 and Bcl2 were also evaluated to confirm the relationship between gene and protein levels. Our data clearly revealed that CD28, p21, MT 1 A, and MT 1B mRNA were highly expressed in the presence of melatonin. Co-culture of CD4＋ T lymphocyte and peritoneal macrophage 7 days after melatonin administration to young and aged mice significantly increased APRIL mRNA, suggesting induction or maintenance of T lymphocyte responses. We also found that the intracellular amount of Ki67 and Bcl2 proteins were significantly upregulated in aged CD4＋ T lymphocytes, suggesting enhancing T cell proliferation and ling-term maintenance of memory T cells. Taken together, we conclude that melatonin supplementation may enhance immunity in aged individuals by upregulating immunosenescence indices in association with T lymphocytes and may be an attractive pharmacological candidate for aged and immunocompromised individuals.
文摘目的探讨中药复方提取物湘A-1（Hu Nan A-1,HNA-1）对猴免疫缺陷病毒（Simian immunodeficiency virus,SIV）慢性感染中国恒河猴胸腺输出功能的影响。方法采用SIVmac239病毒液对8只中国恒河猴进行感染16~21个月,随机分为对照组和治疗组,每组4只。治疗组给予HNA-1灌胃20 m L治疗,每日1次;对照组给予等体积生理盐水灌胃。两组给药2个月。观察两组一般情况、体重,采用实时荧光定量PCR方法检测两组血浆病毒载量,采用流式细胞法检测CD4比例及数量、CD4的初始亚群,实时荧光定量PCR法检测T细胞受体DNA重排删除环（TREC）,常规HE染色后观察胸腺组织的病理情况。分析胸腺组织病变情况与CD4细胞数、初始型CD4细胞数及TREC的关联性。结果治疗后两组体重、病毒载量、CD4比例绝对数比较,差异无统计学意义（P〉0.05）。对照组TREC改变倍数明显呈下降趋势,治疗组总体呈明显的上升趋势,两组间差异有统计学意义（P〈0.05）。两组动物的胸腺组织均可见结构破坏、粉红色无结构样物质填充、结缔组织增多、细胞密度降低、排列紊乱等病理改变,未见明显区别。TREC含量与初始型CD4去除极值后,呈正相关（r=0.926,P=0.001）;而初始型CD4数量与CD4数量呈正相关（r=0.961,P=0.005）。结论检测TREC含量来测定新胸腺迁出细胞数量可作为评价胸腺输出功能的检测方法,且HNA-1可增加胸腺的输出功能,而TREC、初始型CD4数量及胸腺组织病理情况之间存在一定相关关系,在感染晚期尤为明显。
文摘Objective: To evaluate the virological status of ineligible HIV patients for anti-retroviral therapy based on the criterion of CD4+ T lymphocytes rate over than 350/μl of blood. Method: This is a prospective study which was conducted from November 2011 to July 2012 in the tropical and infectious disease department of CHU Sylvanus Olympio of Lomé. All HIV-1 infected patients whose CD4+ T lymphocytes rate was ≥350/μl of blood were retained. The count of CD4+ T lymphocytes was made by cytometer FACSCalibur? flow of BD biosciences and the determination of viral load was achieved by NASBA laboratory method of Biomérieux. Results: We have recruited 102 PLWHA aged between 19 and 58 years with a median of 35 years. Biologically, 102 patients had a T-CD4 rate between 355 and 432/μl of blood. The determination of viral load showed a very high viral replication more than 10,000 copies/ml among all patients and 28 (27.5%) patients had a viral load > 100,000 copies/ml of blood. Conclusion: Our results argue for a reconsideration of the criteria for starting antiretroviral therapy in Togo by including virological data if necessary in patients with T-CD4 rate below 500/μl of blood.
文摘Objective To establish a stable and efficient method of culturing imDCs in vitro,and to explore the effect of GW5074,which blocks ERK1 /2 signal pathway in the process of immature dentritic cells ( imDCs) on inducing differentiation of the naive allogeneic CD4 + T
基金The National Council for ScientificTechnologicalDevelopment (CNPq)+2 种基金 the State of São Paulo Research Foundation (FAPESP) the National Institute ofScienceTechnology of Complex Fluids (INCT-FCx).
文摘Background: Hepcidin is the principal regulator of iron absorption and its tissue distribution. Its correlation with iron homeostasis in individuals infected with human immunodeficiency virus type-1 (HIV-1) treated with different regimens of highly active antiretroviral therapy (HAART) was investigated. Methods: Serum hepcidin levels were determined in 448 volunteers. Of these, 372 were HIV-1-infected individuals, and 93 did not receive HAART (ART-naïve) while 279 received HAART consisting of a non-nucleoside reverse transcriptase inhibitor (NNRTI-based) and protease inhibitors (PI-based);both were used in association with a nucleoside reverse transcriptase inhibitor (NRTI). Seventy-six additional HIV-1 seronegative individuals were enrolled in the study. The following parameters were quantified: hematological parameters, iron biomarkers and markers of infection (CD4+ and CD8+ T-cells), and HIV-1 RNA (viral load). Results: Serum hepcidin, iron and ferritin levels, as well as the marker of infection, CD4+ T-cells, were significantly lower in the ART-naïve group compared with other groups. Additionally, transferrin saturation, iron binding capacity, hemoglobin level and erythrocyte level were not significantly different, and anemia was not observed in the different groups. Conclusions: HIV-1 infection affected serum hepcidin, iron and ferritin levels in the ART-naïve group, and the different HAART regimens restored the levels of hepcidin and iron homeostasis in HIV-1-infected individuals who have undetectable HIV-1 RNA levels.
基金This study was supported by the National Natural Science Foundation of China （No. 81071372）, the National Key Technologies R and D Program for the 11th Five-year Plan （No. 2008ZX10001-006）, the National Key Technologies R and D Program for the 12th Five-year Plan （No. 2012ZX10001003-001）, and the Key Clinical Program of the Ministry of Health （2010-2012）.
文摘Background：Among HlV-infected patients initiating antiretroviral therapy （ART）,early changes in CD4＋ T-cell subsets are well described.However,HIV-infected late presenters initiating treatment present with a suboptimal CD4＋ T-cell reconstitution and remain at a higher risk for AIDS and non-AIDS events.Therefore,factors associated with CD4＋ T-cell reconstitution need to be determined in this population,which will allow designing effective immunotherapeutic strategies.Methods：Thirty-one adult patients with baseline CD4＋ T-cell count 〈350 cells/mm^3 exhibiting viral suppression after ART initiation were followed in the HIV/AIDS research center of Peking Union Medical College Hospital in Beijing,China,from October 2002 to September 2013.Changes in T-cell subsets and associated determinants were measured.Results：Median baseline CD4＋ T-cell count was 70 cells/mm3.We found a biphasic reconstitution ofT-cell subsets and immune activation：a rapid change during the first 6 months followed by a more gradual change over the subsequent 8 years.Baseline CD4＋ T-cell count 〉200 cells/ mm3 in comparison to CD4＋ T-cell count ≤200 cells/mm3 was associated with more complete immune Reconstitution （77.8% vs.27.3% respectively;P =0.017） and normalized CD4/CD8 ratio.We showed that the baseline percentage of naive CD4＋ T-cell was a predictive marker for complete immune reconstitution （area under receiver operating characteristic curve 0.907）,and 12.4% as cutoffvalue had a sensitivity of 84.6% and a specificity of 88.2%.Conclusions：Baseline naive CD4＋ T-cell percentage may serve as a predictive marker for optimal immune reconstitution during long-term therapy.Such study findings suggest that increasing thymic output should represent an avenue to improve patients who are diagnosed late in the course of infection.
