AIM: To determine the relationship between host immunity and the characteristics of viral infection or nucleoside analogues (NAs) themselves in patients with chronic hepatitis B (CHB) receiving NA therapy.
Regulatory T cells （Treg） play important roles in immune system homeostasis, and may also be involved in tumor immunotolerance by suppressing Th1 immune response which is involved in anti-tumor immunity. We have pre...Regulatory T cells （Treg） play important roles in immune system homeostasis, and may also be involved in tumor immunotolerance by suppressing Th1 immune response which is involved in anti-tumor immunity. We have previously reported that immunization with attenuated activated autologous T cells leads to enhanced anti-tumor immunity and upregulated Thl responses in vivo. However, the underlying molecular mechanisms are not well understood. Here we show that Treg function was significantly downregulated in mice that received immunization of attenuated activated autologous T cells. We found that Foxp3 expression decreased in CD4＋CD25＋ T cells from the immunized mice. Moreover, CD4＋CD25＋Foxp3＋ Treg obtained from immunized mice exhibited diminished immunosuppression ability compared to those from naive mice. Further analysis showed that the serum of immunized mice contains a high level ofanti-CD25 antibody （about 30 ng/ml, p〈0.01 vs controls）. Consistent with a role ofanti-CD25 response in the downregulation of Treg, adoptive transfer of serum from immunized mice to naive mice led to a significant decrease in Treg population and function in recipient mice. The triggering of anti-CD25 response in immunized mice can be explained by the fact that CD25 was induced to a high level in the ConA activated autologous T cells used for immunization. Our results demonstrate for the first time that immunization with attenuated activated autologous T cells evokes anti-CD25 antibody production, which leads to impeded CD4＋CD25＋Foxp3＋ Treg expansion and function in vivo. We suggest that dampened Treg function likely contributes to enhanced Thl response in immunized mice and is at least part of the mechanism underlying the boosted anti-tumor immunity.展开更多
AIM: To assess the absolute number of T-regulatory cells (Tregs; CD4+CD25+Foxp3+) in the peripheral blood of gastric and colorectal cancer patients. METHODS: We enrolled 70 cancer patients (33 gastric cancer, 37 color...AIM: To assess the absolute number of T-regulatory cells (Tregs; CD4+CD25+Foxp3+) in the peripheral blood of gastric and colorectal cancer patients. METHODS: We enrolled 70 cancer patients (33 gastric cancer, 37 colorectal cancer) and 17 healthy volunteers. The CD3+CD4+ lymphocytes and CD4+CD25+Foxp3+ Tregs in the peripheral blood were analyzed with flow cytometry. The absolute numbers of Tregs were calculated based on the CD4+CD25+Foxp3+ cells percent-age of CD3+CD4+ cells and the absolute numbers of CD3+CD4+ cells per microliter. RESULTS: The mean number of CD4+CD25+Foxp3+ cells per microliter in colorectal cancer patients was 15.7 (SD: 21.8), for gastric cancer patients 12.2 (SD: 14.3), and for controls 17.5 (SD: 11.4). The absolute number of Tregs was significantly lower in gastric cancer patients than in controls (P = 0.026). There was no statistically significant difference for gastric vs colorectal cancer or colorectal cancer vs controls. The absolute number of Tregs was also significantly depressed in N+ vs Ncancer patients [22.0 (27.7) vs 10.1 (9.0), P = 0.013], and in the subgroup of gastric cancer patients [30.3 (27.6) vs 9.6 (8.0), P = 0.003]. No statistical difference was observed in the proportion of Tregs in the CD4+ population between the groups. CONCLUSION: The absolute number of Tregs in peripheral blood of gastric cancer but not colorectal cancer patients was significantly decreased in comparison with that in healthy controls.展开更多
目的：探讨成人原发免疫性血小板减少症（ ITP）患者外周血中Th9、Th17和CD4＋CD25＋Foxp3＋调节性T细胞及相关细胞因子的表达水平及意义。方法采用流式细胞仪检测47例ITP患者外周血Th9、Th17和Treg细胞的表达率,采用酶联免疫吸附方法（...目的：探讨成人原发免疫性血小板减少症（ ITP）患者外周血中Th9、Th17和CD4＋CD25＋Foxp3＋调节性T细胞及相关细胞因子的表达水平及意义。方法采用流式细胞仪检测47例ITP患者外周血Th9、Th17和Treg细胞的表达率,采用酶联免疫吸附方法（ ELISA）检测外周血中细胞因子IL-9、IL-17、TGF-β等的表达水平。结果（1）ITP组患者外周血Th9、Th17细胞比例及细胞因子IL-9、IL-17浓度均明显高于健康对照组[（1.27±0.31）% vs （0.71±0.26）%, P〈0.05；（2.01±0.42）% vs （0.97±0.32）%, P〈0.05。（26.52±7.48） ng/L vs （16.16±5.27） ng/L, P〈0.05；（10.97±3.94） ng/L vs （7.14±2.73） ng/L, P〈0.05]。 CD4＋CD25＋Foxp3＋细胞比例及细胞因子TGF-β浓度明显低于对照组[（4.69±0.85）% vs （7.16±1.92）%,P〈0.05。（3.76±1.28）μg/L vs （6.41±1.83）μg/L,P〈0.05]。（2）相关性分析：患者Th9、Th17细胞比例及IL-9、IL-17浓度与血小板计数负相关（γs=-0.349,P=0.037；γs=-0.392,P=0.031；γs=-0.436,P=0.014；γs=-0.401,P=0.027）；患者Treg细胞比例及TGF-β浓度与血小板计数正相关（γs=0.411,P=0.024；γs=0.407,P=0.026）。结论成人原发免疫性血小板减少症患者 Th9、Th17与 CD4＋CD25＋Foxp3＋调节性 T 细胞比例失衡,血清IL-9、IL-17和TGF-β水平改变,这些原因可能参与成人原发免疫性血小板减少症的免疫发病过程。展开更多
目的比较宫颈局部微环境高危型人乳头状瘤病毒载量(HR-HPV DNA)和CD4+CD25+Foxp3+调节性T细胞(Treg)的同步变化,探讨HR-HPV病毒复制和宫颈病变进展两者同时对Treg细胞的影响。方法将304例HR-HPV持续感染者依宫颈病变的不同分为5组:宫颈...目的比较宫颈局部微环境高危型人乳头状瘤病毒载量(HR-HPV DNA)和CD4+CD25+Foxp3+调节性T细胞(Treg)的同步变化,探讨HR-HPV病毒复制和宫颈病变进展两者同时对Treg细胞的影响。方法将304例HR-HPV持续感染者依宫颈病变的不同分为5组:宫颈上皮内瘤变(CIN)Ⅰ、CINⅡ、CINⅢ、宫颈癌和慢性宫颈炎,采用PCR荧光法检测宫颈分泌物HPV-DNA,应用流式细胞仪CD4+CD25+Foxp3+设门方法对宫颈刷检物中的CD4+CD25+Treg细胞相对计数,对数据资料进行统计学分析。结果(1)宫颈局部Treg细胞表达在不同程度的宫颈病变和不同拷贝数的病毒载量之间比较差异均有显著性(F=24.93,109.86,P<0.05),进一步的两两比较显示,Treg细胞的水平变化在慢性宫颈炎和CINⅠ之间以及低载量(HPV DNA 104~105copies/m L)和中载量(HPV DNA 105~106copies/m L)之间差异无统计学意义(P>0.05),其他组组间比较差异有统计学意义(P<0.05);(2)以Treg细胞水平变化为变量,宫颈病变和病毒载量为因子的交互效应显著(F=3.39,P<0.05),不同的宫颈病变,HR-HPV病毒载量对Treg表达的影响大小不一,总体呈现随着宫颈病变程度加重,HR-HPV病毒拷贝数升高,Treg细胞表达Foxp3+逐步上升的趋势;(3)宫颈癌患者高表达CD4+CD25+Foxp3+Treg细胞,但表达水平波动范围大,数值分布最为分散。结论宫颈局部微环境CD4+CD25+Foxp3+Treg细胞的免疫抑制功能在不同宫颈病变和不同HR-HPV DNA中可能通过双向性调节,影响宫颈病变转归,就整体变化而言,Treg细胞、HR-HPV载量、宫颈病变三者呈相向的进展趋向。展开更多
AIM To investigate T-cell activation, the percentage of peripheral T regulatory cells(Tregs), Th17 cells and the circulating cytokine profile in systemic sclerosis(SSc).METHODS We enrolled a total of 24 SSc patients a...AIM To investigate T-cell activation, the percentage of peripheral T regulatory cells(Tregs), Th17 cells and the circulating cytokine profile in systemic sclerosis(SSc).METHODS We enrolled a total of 24 SSc patients and 16 healthy controls in the study and divided the patients as having diffuse cutaneous SSc(dc SSc, n = 13) or limited cutaneous SSc(lc SSc, n = 11). We performed a further subdivision of the patients regarding the stage of the disease-early, intermediate or late. Peripheral venous blood samples were collected from all subjects. We performed flow cytometric analysis of the activationcapacity of T-lymphocytes upon stimulation with PHA-M and of the percentage of peripheral Tregs and Th17 cells in both patients and healthy controls. We used ELISA to quantitate serum levels of human interleukin(IL)-6, IL-10, tissue growth factor-β1(TGF-β1), and IL-17 A.RESULTS We identified a decreased percentage of CD3+CD69+ cells in PHA-stimulated samples from SSc patients in comparison with healthy controls(13.35% ± 2.90% vs 37.03% ± 2.33%, P < 0.001). However, we did not establish a correlation between the down-regulated CD3+CD69+ cells and the clinical subset, nor regarding the stage of the disease. The activated CD4+CD25+ peripheral lymphocytes were represented in decreased percentage in patients when compared to controls(6.30% ± 0.68% vs 9.36% ± 1.08%, P = 0.016). Regarding the forms of the disease, dc SSc patients demonstrated lower frequency of CD4+CD25+ T cells against healthy subjects(5.95% ± 0.89% vs 9.36% ± 1.08%, P = 0.025). With regard to Th17 cells, our patients demonstrated increased percentage in comparison with controls(18.13% ± 1.55% vs 13.73% ± 1.21%, P = 0.031). We detected up-regulated Th17 cells within the lc SSc subset against controls(20.46% ± 2.41% vs 13.73% ± 1.21%, P = 0.025), nevertheless no difference was found between dc SSc and lc SSc patients. Flow cytometric analysis revealed an increased percentage of CD4+CD25-Foxp3+ in dc SSc patients compared to controls(10.94% ± 1.65% 展开更多
调节性T细胞(regulatory T cell,Treg)是一群胸腺来源的具有免疫抑制功能的T淋巴细胞,其与自身免疫疾病的发生、外周免疫耐受以及抗感染免疫、肿瘤免疫、移植免疫、变态反应等许多病理性免疫过程有着极其重要的关系。天然型调节性T细胞(...调节性T细胞(regulatory T cell,Treg)是一群胸腺来源的具有免疫抑制功能的T淋巴细胞,其与自身免疫疾病的发生、外周免疫耐受以及抗感染免疫、肿瘤免疫、移植免疫、变态反应等许多病理性免疫过程有着极其重要的关系。天然型调节性T细胞(natural Treg,n Treg)或称胸腺调节性T细胞(thymus regulatory T cell,t Treg)是调节性T细胞群中很重要的一个亚群。本文将对这一主要亚群及其分化、发育、增殖等过程和相关调控机制进行综述。展开更多
基金Supported by The Shanghai Natural Science Fund,No.09ZR1400500the National Natural Science Foundation of China,No.30972600+1 种基金the GuangHui Fund of Hepatitis Prevention Fund Committee China,No.GHZ20100204the Shanghai Health Bureau Fund,No.2012092
文摘AIM: To determine the relationship between host immunity and the characteristics of viral infection or nucleoside analogues (NAs) themselves in patients with chronic hepatitis B (CHB) receiving NA therapy.
基金This work was supported by National Natural Science Foundation of China(No.30671945)Science and Technology Commission of Shanghai Municipality(Nos.06JC14044,05ZR14055,054319928,04DZ14902)+2 种基金Shanghai Municipal Education(No.05BZ26)Shanghai Leading Academic Discipline Project(T0206)Science Foundation of Shanghai Institute of Immunology(No.07-A04,to Ningli Li).
文摘Regulatory T cells （Treg） play important roles in immune system homeostasis, and may also be involved in tumor immunotolerance by suppressing Th1 immune response which is involved in anti-tumor immunity. We have previously reported that immunization with attenuated activated autologous T cells leads to enhanced anti-tumor immunity and upregulated Thl responses in vivo. However, the underlying molecular mechanisms are not well understood. Here we show that Treg function was significantly downregulated in mice that received immunization of attenuated activated autologous T cells. We found that Foxp3 expression decreased in CD4＋CD25＋ T cells from the immunized mice. Moreover, CD4＋CD25＋Foxp3＋ Treg obtained from immunized mice exhibited diminished immunosuppression ability compared to those from naive mice. Further analysis showed that the serum of immunized mice contains a high level ofanti-CD25 antibody （about 30 ng/ml, p〈0.01 vs controls）. Consistent with a role ofanti-CD25 response in the downregulation of Treg, adoptive transfer of serum from immunized mice to naive mice led to a significant decrease in Treg population and function in recipient mice. The triggering of anti-CD25 response in immunized mice can be explained by the fact that CD25 was induced to a high level in the ConA activated autologous T cells used for immunization. Our results demonstrate for the first time that immunization with attenuated activated autologous T cells evokes anti-CD25 antibody production, which leads to impeded CD4＋CD25＋Foxp3＋ Treg expansion and function in vivo. We suggest that dampened Treg function likely contributes to enhanced Thl response in immunized mice and is at least part of the mechanism underlying the boosted anti-tumor immunity.
基金Supported by Ministry of Science and Higher Education of Poland Grants 2P05C 001 29 and K/PBW/000421
文摘AIM: To assess the absolute number of T-regulatory cells (Tregs; CD4+CD25+Foxp3+) in the peripheral blood of gastric and colorectal cancer patients. METHODS: We enrolled 70 cancer patients (33 gastric cancer, 37 colorectal cancer) and 17 healthy volunteers. The CD3+CD4+ lymphocytes and CD4+CD25+Foxp3+ Tregs in the peripheral blood were analyzed with flow cytometry. The absolute numbers of Tregs were calculated based on the CD4+CD25+Foxp3+ cells percent-age of CD3+CD4+ cells and the absolute numbers of CD3+CD4+ cells per microliter. RESULTS: The mean number of CD4+CD25+Foxp3+ cells per microliter in colorectal cancer patients was 15.7 (SD: 21.8), for gastric cancer patients 12.2 (SD: 14.3), and for controls 17.5 (SD: 11.4). The absolute number of Tregs was significantly lower in gastric cancer patients than in controls (P = 0.026). There was no statistically significant difference for gastric vs colorectal cancer or colorectal cancer vs controls. The absolute number of Tregs was also significantly depressed in N+ vs Ncancer patients [22.0 (27.7) vs 10.1 (9.0), P = 0.013], and in the subgroup of gastric cancer patients [30.3 (27.6) vs 9.6 (8.0), P = 0.003]. No statistical difference was observed in the proportion of Tregs in the CD4+ population between the groups. CONCLUSION: The absolute number of Tregs in peripheral blood of gastric cancer but not colorectal cancer patients was significantly decreased in comparison with that in healthy controls.
文摘目的：探讨成人原发免疫性血小板减少症（ ITP）患者外周血中Th9、Th17和CD4＋CD25＋Foxp3＋调节性T细胞及相关细胞因子的表达水平及意义。方法采用流式细胞仪检测47例ITP患者外周血Th9、Th17和Treg细胞的表达率,采用酶联免疫吸附方法（ ELISA）检测外周血中细胞因子IL-9、IL-17、TGF-β等的表达水平。结果（1）ITP组患者外周血Th9、Th17细胞比例及细胞因子IL-9、IL-17浓度均明显高于健康对照组[（1.27±0.31）% vs （0.71±0.26）%, P〈0.05；（2.01±0.42）% vs （0.97±0.32）%, P〈0.05。（26.52±7.48） ng/L vs （16.16±5.27） ng/L, P〈0.05；（10.97±3.94） ng/L vs （7.14±2.73） ng/L, P〈0.05]。 CD4＋CD25＋Foxp3＋细胞比例及细胞因子TGF-β浓度明显低于对照组[（4.69±0.85）% vs （7.16±1.92）%,P〈0.05。（3.76±1.28）μg/L vs （6.41±1.83）μg/L,P〈0.05]。（2）相关性分析：患者Th9、Th17细胞比例及IL-9、IL-17浓度与血小板计数负相关（γs=-0.349,P=0.037；γs=-0.392,P=0.031；γs=-0.436,P=0.014；γs=-0.401,P=0.027）；患者Treg细胞比例及TGF-β浓度与血小板计数正相关（γs=0.411,P=0.024；γs=0.407,P=0.026）。结论成人原发免疫性血小板减少症患者 Th9、Th17与 CD4＋CD25＋Foxp3＋调节性 T 细胞比例失衡,血清IL-9、IL-17和TGF-β水平改变,这些原因可能参与成人原发免疫性血小板减少症的免疫发病过程。
文摘目的比较宫颈局部微环境高危型人乳头状瘤病毒载量(HR-HPV DNA)和CD4+CD25+Foxp3+调节性T细胞(Treg)的同步变化,探讨HR-HPV病毒复制和宫颈病变进展两者同时对Treg细胞的影响。方法将304例HR-HPV持续感染者依宫颈病变的不同分为5组:宫颈上皮内瘤变(CIN)Ⅰ、CINⅡ、CINⅢ、宫颈癌和慢性宫颈炎,采用PCR荧光法检测宫颈分泌物HPV-DNA,应用流式细胞仪CD4+CD25+Foxp3+设门方法对宫颈刷检物中的CD4+CD25+Treg细胞相对计数,对数据资料进行统计学分析。结果(1)宫颈局部Treg细胞表达在不同程度的宫颈病变和不同拷贝数的病毒载量之间比较差异均有显著性(F=24.93,109.86,P<0.05),进一步的两两比较显示,Treg细胞的水平变化在慢性宫颈炎和CINⅠ之间以及低载量(HPV DNA 104~105copies/m L)和中载量(HPV DNA 105~106copies/m L)之间差异无统计学意义(P>0.05),其他组组间比较差异有统计学意义(P<0.05);(2)以Treg细胞水平变化为变量,宫颈病变和病毒载量为因子的交互效应显著(F=3.39,P<0.05),不同的宫颈病变,HR-HPV病毒载量对Treg表达的影响大小不一,总体呈现随着宫颈病变程度加重,HR-HPV病毒拷贝数升高,Treg细胞表达Foxp3+逐步上升的趋势;(3)宫颈癌患者高表达CD4+CD25+Foxp3+Treg细胞,但表达水平波动范围大,数值分布最为分散。结论宫颈局部微环境CD4+CD25+Foxp3+Treg细胞的免疫抑制功能在不同宫颈病变和不同HR-HPV DNA中可能通过双向性调节,影响宫颈病变转归,就整体变化而言,Treg细胞、HR-HPV载量、宫颈病变三者呈相向的进展趋向。
文摘AIM To investigate T-cell activation, the percentage of peripheral T regulatory cells(Tregs), Th17 cells and the circulating cytokine profile in systemic sclerosis(SSc).METHODS We enrolled a total of 24 SSc patients and 16 healthy controls in the study and divided the patients as having diffuse cutaneous SSc(dc SSc, n = 13) or limited cutaneous SSc(lc SSc, n = 11). We performed a further subdivision of the patients regarding the stage of the disease-early, intermediate or late. Peripheral venous blood samples were collected from all subjects. We performed flow cytometric analysis of the activationcapacity of T-lymphocytes upon stimulation with PHA-M and of the percentage of peripheral Tregs and Th17 cells in both patients and healthy controls. We used ELISA to quantitate serum levels of human interleukin(IL)-6, IL-10, tissue growth factor-β1(TGF-β1), and IL-17 A.RESULTS We identified a decreased percentage of CD3+CD69+ cells in PHA-stimulated samples from SSc patients in comparison with healthy controls(13.35% ± 2.90% vs 37.03% ± 2.33%, P < 0.001). However, we did not establish a correlation between the down-regulated CD3+CD69+ cells and the clinical subset, nor regarding the stage of the disease. The activated CD4+CD25+ peripheral lymphocytes were represented in decreased percentage in patients when compared to controls(6.30% ± 0.68% vs 9.36% ± 1.08%, P = 0.016). Regarding the forms of the disease, dc SSc patients demonstrated lower frequency of CD4+CD25+ T cells against healthy subjects(5.95% ± 0.89% vs 9.36% ± 1.08%, P = 0.025). With regard to Th17 cells, our patients demonstrated increased percentage in comparison with controls(18.13% ± 1.55% vs 13.73% ± 1.21%, P = 0.031). We detected up-regulated Th17 cells within the lc SSc subset against controls(20.46% ± 2.41% vs 13.73% ± 1.21%, P = 0.025), nevertheless no difference was found between dc SSc and lc SSc patients. Flow cytometric analysis revealed an increased percentage of CD4+CD25-Foxp3+ in dc SSc patients compared to controls(10.94% ± 1.65%
文摘调节性T细胞(regulatory T cell,Treg)是一群胸腺来源的具有免疫抑制功能的T淋巴细胞,其与自身免疫疾病的发生、外周免疫耐受以及抗感染免疫、肿瘤免疫、移植免疫、变态反应等许多病理性免疫过程有着极其重要的关系。天然型调节性T细胞(natural Treg,n Treg)或称胸腺调节性T细胞(thymus regulatory T cell,t Treg)是调节性T细胞群中很重要的一个亚群。本文将对这一主要亚群及其分化、发育、增殖等过程和相关调控机制进行综述。
