AIM:To assess the peripheral T lymphocyte subsets in chronic hepatitis B virus(HBV) infection,and their dynamics in response to adefovir dipivoxil monotherapy.METHODS:Proportions and absolute counts of peripheral natu...AIM:To assess the peripheral T lymphocyte subsets in chronic hepatitis B virus(HBV) infection,and their dynamics in response to adefovir dipivoxil monotherapy.METHODS:Proportions and absolute counts of peripheral natural killer cells,B cells,CD8+,CD4+,CD8+ CD38+,CD8+CD28+ and CD4+CD28+ T cells were determined using three-color flow cytometry in chronic hepatitis B patients(n = 35),HBV carriers(n = 25) and healthy controls(n = 35).Adefovir dipivoxil was initiated in 17 chronic hepatitis B patients who were regularly followed for 72 wk,during which period the T cell subsets and serum viral load were measured at each follow-up point.RESULTS:The peripheral CD4+ T cell counts and CD8+ T cell counts decreased in chronic HBV infection.In chronic hepatitis B patients,proportions of CD8+CD38+ T cells were 62.0% ± 14.7%,much higher than those of HBV carriers and healthy con-trols.In the 13 hepatitis B patients who were treated and responded to adefovir dipivoxil,proportions of CD8+CD38+ T cells decreased from 53.9% ± 18.4% pre-therapy to 20.1% ± 11.3% by week 72(P < 0.001),concomitant with viral load decline(HBV DNA fell from 7.31 to 3 log copies/mL).CD8+ T cell counts also underwent an average increase of 218 cells/μL by the end of 72-wk treatment.In those who failed the therapy,the CD8+CD38+ T cell population had more fluctuations.CONCLUSION:CD8+ T cells abnormally activated in chronic HBV infection can be partially reversed by antiviral therapy.HBV-associated immune activation may be a crucial part of the pathogenesis and a promising target of treatment.展开更多
Objective:To investigate the changes of Mg^(2+) levels in serum and peripheral blood mononuclear cells(PBMCs)of patients with COVID-19 and its effects on the functions of CD8^(+)T lymphocytes and NK cells.Methods:A to...Objective:To investigate the changes of Mg^(2+) levels in serum and peripheral blood mononuclear cells(PBMCs)of patients with COVID-19 and its effects on the functions of CD8^(+)T lymphocytes and NK cells.Methods:A total of 165 COVID-19 patients hospitalized in Ezhou Central Hospital from January 20 to February 20,2020 were divided into mild/common group(98 cases)and severe/critical group(67 cases).At the same time,34 healthy persons were selected as the control group.Peripheral blood was collected and PBMCs were isolated,the level of Mg^(2+) in serum and PBMCs was detected.The subsets of CD8^(+)T lymphocytes and NK cell and the expression levels of their surface inhibitory molecular PD-1 and activator molecular NKG2D were detected by flow cytometry.The correlation between Mg^(2+) concentration and the expression levels of PD-1 and NKG2D was also analyzed.Results:Compared with the control group,the concentration of Mg^(2+) in serum and PBMCs,the counts of CD8^(+)T lymphocytes and NK cell in patients with mild/common and severe/critical groups were significantly reduced(P<0.05),while the expression level of surface inhibitory molecular PD-1 were significantly increased(P<0.05),while the expression level of the activation molecule NKG2D were significantly decreased(P<0.05).However,the changes of the above indicators in patients with severe/critical group were greater than those in the mild/common group(P<0.05).In addition,the Mg^(2+) concentration in COVID-19 patients was negatively correlated with the expression level of PD-1 on CD8^(+)T lymphocytes and NK cells(P<0.05),and positively correlated with the expression levels of NKG2D(P<0.05).Conclusion:The concentration of Mg^(2+) in the serum and PBMCs of COVID-19 patients is significantly reduced,which may cause the function of CD8^(+)T lymphocytes and NK cells to be inhibited.展开更多
Now molecular epidemiology was meaningful. On the surface of the tumor, cells will express its antigen specific as a tumor cell (example: TSA, tumor specific antigen) and can induce cellular immune response. The resul...Now molecular epidemiology was meaningful. On the surface of the tumor, cells will express its antigen specific as a tumor cell (example: TSA, tumor specific antigen) and can induce cellular immune response. The result of interactions between group antigens with the immune system cells of the body will cause a rise in the expression of lymphocytes CD8+. The aim of this research is to find out differences in the number of lymphocytes CD8+ expression between benign and malignant tissues. This research is a laboratory experiment with the approach of cross sectional. Samples are taken from benign and malignant tissue biopsy of the breast and cervical uterine that were got from anatomical pathology laboratory, period January to February 2004. A technique using random sampling, is sample acquiring 30 benign cancer and 30 malignant of the breast or cervical uterine. To find out the significance of the difference in the number of lymphocytes CD8+ between benign and malignant of breast or cervical uterine, we used a statistical analysis Anova in SPSS for Windows 15.0 program. In this research the number of lymphocytes average in the benign cancer is 2.9667 cells (breast) and 4.2667 cells (cervical uterine), on the other side malignant tissue of 23.8000 cells (breast) and 25.0333 cells (cervical uterine). From the statistical analyses with Anova the number of lymphocytes CD8+ was very significant differences between benign and malignant of the breast or cervical uterine tissue (p < 0.001). The conclusion of this research is that there is a significant increase of the number of lymphocytes CD8+ expression in cancer tissue.展开更多
目的以雌性和雄性非肥胖糖尿病(nonobese diabetic,NOD)小鼠以及健康对照癌症研究所(institute for cancer research,ICR)小鼠为研究对象,比较分析初始、效应、记忆、耗竭以及调节性CD8^(+)T细胞分化亚群差异,探讨1型糖尿病(type 1 diab...目的以雌性和雄性非肥胖糖尿病(nonobese diabetic,NOD)小鼠以及健康对照癌症研究所(institute for cancer research,ICR)小鼠为研究对象,比较分析初始、效应、记忆、耗竭以及调节性CD8^(+)T细胞分化亚群差异,探讨1型糖尿病(type 1 diabetes,T1D)背景下的性别因素对CD8^(+)T细胞分化命运的影响。方法采用流式细胞术检测雌雄NOD小鼠脾脏、胰腺引流淋巴结(pancreatic draining lymph nodes,pLN)、胰腺浸润淋巴细胞(pancreas-infiltrating lymphocytes,PIL)、初始T细胞(naive T cells,T_(N))、中枢记忆T细胞(central memory T cells,T_(CM))、效应T细胞(effector T cells,T_(EFF))、效应前体样T细胞(effector precursor T cells,T_(EP))、耗竭T细胞(exhausted T cells,T_(EX))、耗竭前体T细胞(precursor exhausted T cells,T_(PEX))以及调节性T细胞(regulatory T cells,Tregs)等CD8^(+)T细胞分化亚群的频率和表型差异。结果与雄性NOD小鼠比较,雌性NOD小鼠pLN及PIL中IFN-γ^(+)、CD107a^(+)和CCL5^(+)CD8^(+)T_(EFF)频率显著升高(P<0.01,P<0.05,P<0.05),同时脾脏中CD8^(+)T_(N)、CD8^(+)T_(CM)、CD8^(+)T_(EX)、CD8^(+)T_(PEX)和CD122^(+)CD8^(+)Tregs亚群的频率均显著降低(P<0.01,P<0.01,P<0.01,P<0.01,P<0.001);而雌性和雄性ICR小鼠体内除CD122^(+)CD8^(+)Tregs差异变化与NOD小鼠一致(P<0.05),其余上述各CD8^(+)T细胞分化亚群无显著差异。结论雄激素可能通过抑制记忆T细胞向效应T细胞分化,同时促进效应T细胞功能耗竭,导致雌雄发病率差异。展开更多
基金Supported by National Key Technologies R&D Program for the 11th Five-year Plan,No. 2008ZX10001-006
文摘AIM:To assess the peripheral T lymphocyte subsets in chronic hepatitis B virus(HBV) infection,and their dynamics in response to adefovir dipivoxil monotherapy.METHODS:Proportions and absolute counts of peripheral natural killer cells,B cells,CD8+,CD4+,CD8+ CD38+,CD8+CD28+ and CD4+CD28+ T cells were determined using three-color flow cytometry in chronic hepatitis B patients(n = 35),HBV carriers(n = 25) and healthy controls(n = 35).Adefovir dipivoxil was initiated in 17 chronic hepatitis B patients who were regularly followed for 72 wk,during which period the T cell subsets and serum viral load were measured at each follow-up point.RESULTS:The peripheral CD4+ T cell counts and CD8+ T cell counts decreased in chronic HBV infection.In chronic hepatitis B patients,proportions of CD8+CD38+ T cells were 62.0% ± 14.7%,much higher than those of HBV carriers and healthy con-trols.In the 13 hepatitis B patients who were treated and responded to adefovir dipivoxil,proportions of CD8+CD38+ T cells decreased from 53.9% ± 18.4% pre-therapy to 20.1% ± 11.3% by week 72(P < 0.001),concomitant with viral load decline(HBV DNA fell from 7.31 to 3 log copies/mL).CD8+ T cell counts also underwent an average increase of 218 cells/μL by the end of 72-wk treatment.In those who failed the therapy,the CD8+CD38+ T cell population had more fluctuations.CONCLUSION:CD8+ T cells abnormally activated in chronic HBV infection can be partially reversed by antiviral therapy.HBV-associated immune activation may be a crucial part of the pathogenesis and a promising target of treatment.
文摘Objective:To investigate the changes of Mg^(2+) levels in serum and peripheral blood mononuclear cells(PBMCs)of patients with COVID-19 and its effects on the functions of CD8^(+)T lymphocytes and NK cells.Methods:A total of 165 COVID-19 patients hospitalized in Ezhou Central Hospital from January 20 to February 20,2020 were divided into mild/common group(98 cases)and severe/critical group(67 cases).At the same time,34 healthy persons were selected as the control group.Peripheral blood was collected and PBMCs were isolated,the level of Mg^(2+) in serum and PBMCs was detected.The subsets of CD8^(+)T lymphocytes and NK cell and the expression levels of their surface inhibitory molecular PD-1 and activator molecular NKG2D were detected by flow cytometry.The correlation between Mg^(2+) concentration and the expression levels of PD-1 and NKG2D was also analyzed.Results:Compared with the control group,the concentration of Mg^(2+) in serum and PBMCs,the counts of CD8^(+)T lymphocytes and NK cell in patients with mild/common and severe/critical groups were significantly reduced(P<0.05),while the expression level of surface inhibitory molecular PD-1 were significantly increased(P<0.05),while the expression level of the activation molecule NKG2D were significantly decreased(P<0.05).However,the changes of the above indicators in patients with severe/critical group were greater than those in the mild/common group(P<0.05).In addition,the Mg^(2+) concentration in COVID-19 patients was negatively correlated with the expression level of PD-1 on CD8^(+)T lymphocytes and NK cells(P<0.05),and positively correlated with the expression levels of NKG2D(P<0.05).Conclusion:The concentration of Mg^(2+) in the serum and PBMCs of COVID-19 patients is significantly reduced,which may cause the function of CD8^(+)T lymphocytes and NK cells to be inhibited.
文摘Now molecular epidemiology was meaningful. On the surface of the tumor, cells will express its antigen specific as a tumor cell (example: TSA, tumor specific antigen) and can induce cellular immune response. The result of interactions between group antigens with the immune system cells of the body will cause a rise in the expression of lymphocytes CD8+. The aim of this research is to find out differences in the number of lymphocytes CD8+ expression between benign and malignant tissues. This research is a laboratory experiment with the approach of cross sectional. Samples are taken from benign and malignant tissue biopsy of the breast and cervical uterine that were got from anatomical pathology laboratory, period January to February 2004. A technique using random sampling, is sample acquiring 30 benign cancer and 30 malignant of the breast or cervical uterine. To find out the significance of the difference in the number of lymphocytes CD8+ between benign and malignant of breast or cervical uterine, we used a statistical analysis Anova in SPSS for Windows 15.0 program. In this research the number of lymphocytes average in the benign cancer is 2.9667 cells (breast) and 4.2667 cells (cervical uterine), on the other side malignant tissue of 23.8000 cells (breast) and 25.0333 cells (cervical uterine). From the statistical analyses with Anova the number of lymphocytes CD8+ was very significant differences between benign and malignant of the breast or cervical uterine tissue (p < 0.001). The conclusion of this research is that there is a significant increase of the number of lymphocytes CD8+ expression in cancer tissue.
文摘目的研究长链非编码RNA(long non-coding RNA,LncRNA)LINC01137在非小细胞肺癌(nonsmall cell lung cancer,NSCLC)免疫逃逸中的生物学功能及其潜在的调节机制。方法采集24例健康志愿者和24例NSCLC患者血液样本,并收集NSCLC肿瘤组织和癌旁组织检测LINC01137水平。利用Starbase数据库预测LINC01137与miR-22-3p的结合位点,荧光素酶报告基因分析进行验证。采用A549细胞来源的外泌体和/或sh-LINC01137干扰序列转染A549细胞,检测细胞增殖和侵袭能力;收集转染后的细胞上清液培养CD8^(+)T细胞,检测CD8^(+)T细胞耗竭标志物干扰素-γ(interfereron-γ,IFN-γ)、肿瘤坏死因子-α(tumor necrosis factor-α,TNF-α)、颗粒霉素B(granzyme B)和白细胞介素-2(interleukin-2,IL-2)水平,以及PD-1+Tim3^(+)CD8^(+)T细胞百分比。采用外泌体和/或miR-22-3p模拟物(miR-22-3p mimic)转染CD8^(+)T细胞,检测PD-1蛋白水平。结果与癌旁组织相比,NSCLC肿瘤组织中LINC01137表达(3.357±0.548 vs 1.011±0.371)明显升高;与健康志愿者相比,NSCLC患者外周血LINC01137表达(3.216±0.342 vs 1.007±0.313)亦明显升高,差异具有统计学意义(t=-17.367,-17.147,均P<0.001)。肿瘤组织LINC01137表达与外周血中LINC01137表达呈正相关(r=0.755,P<0.05)。在A549细胞来源的外泌体中LINC01137显著富集。与Exo+sh-NC组相比,Exo+sh-LINC01137组细胞活力(65.852%±4.715%vs 100.153%±11.934%)及细胞侵袭(21.464%±3.481%vs 43.126%±1.447%)能力显著降低,差异具有统计学意义(t=4.630,9.953,均P<0.01)。NSCLC患者外周血中LINC01137表达和CD8^(+)T细胞百分比呈负相关(r=-0.520,P<0.05)。与Exo+sh-NC组相比,Exo+sh-LINC01137组IFN-γ(3865.314±543.852 pg/ml vs 1786.971±105.982 pg/ml),TNF-α(4631.930±510.715pg/ml vs 1973.242±379.623pg/ml),Granzyme B(3876.496±312.438pg/ml vs 1879.439±287.584pg/ml)和IL-2 mRNA水平(3.286±0.437 vs 1.015±0.314)升高,PD-1+Tim3^(+)CD8^(+)T细胞百分比(7.680%±2.185%vs 18.952%±3.216%)降低,差异具有统计学意义(t=-6.497,-7.237,-8.146,-7.310,5.021,均P<0.01)。miR-22-3p是LINC01137的靶基因。与Exo+NC mimic组相比,Exo+miR-22-3p组PD-1蛋白水平(0.384±0.087 vs 1.003±0.147)显著降低,差异有统计学意义(t=6.277,P<0.01)。结论NSCLC患者肿瘤组织及外周血中LINC01137表达显著上调;NSCLC细胞来源的外泌体中LINC01137通过靶向CD8^(+)T细胞中miR-22-3p并抑制其表达,诱导CD8^(+)T细胞耗竭,促进NSCLC细胞免疫逃逸。
文摘目的以雌性和雄性非肥胖糖尿病(nonobese diabetic,NOD)小鼠以及健康对照癌症研究所(institute for cancer research,ICR)小鼠为研究对象,比较分析初始、效应、记忆、耗竭以及调节性CD8^(+)T细胞分化亚群差异,探讨1型糖尿病(type 1 diabetes,T1D)背景下的性别因素对CD8^(+)T细胞分化命运的影响。方法采用流式细胞术检测雌雄NOD小鼠脾脏、胰腺引流淋巴结(pancreatic draining lymph nodes,pLN)、胰腺浸润淋巴细胞(pancreas-infiltrating lymphocytes,PIL)、初始T细胞(naive T cells,T_(N))、中枢记忆T细胞(central memory T cells,T_(CM))、效应T细胞(effector T cells,T_(EFF))、效应前体样T细胞(effector precursor T cells,T_(EP))、耗竭T细胞(exhausted T cells,T_(EX))、耗竭前体T细胞(precursor exhausted T cells,T_(PEX))以及调节性T细胞(regulatory T cells,Tregs)等CD8^(+)T细胞分化亚群的频率和表型差异。结果与雄性NOD小鼠比较,雌性NOD小鼠pLN及PIL中IFN-γ^(+)、CD107a^(+)和CCL5^(+)CD8^(+)T_(EFF)频率显著升高(P<0.01,P<0.05,P<0.05),同时脾脏中CD8^(+)T_(N)、CD8^(+)T_(CM)、CD8^(+)T_(EX)、CD8^(+)T_(PEX)和CD122^(+)CD8^(+)Tregs亚群的频率均显著降低(P<0.01,P<0.01,P<0.01,P<0.01,P<0.001);而雌性和雄性ICR小鼠体内除CD122^(+)CD8^(+)Tregs差异变化与NOD小鼠一致(P<0.05),其余上述各CD8^(+)T细胞分化亚群无显著差异。结论雄激素可能通过抑制记忆T细胞向效应T细胞分化,同时促进效应T细胞功能耗竭,导致雌雄发病率差异。
