Background At the end of 2005, 650 000 people lived with human immunodeficiency virus type-1 （HIV-1） in China, of whom 75 000 were AIDS patients. Many AIDS patients received highly active antiretroviral therapy （HA...Background At the end of 2005, 650 000 people lived with human immunodeficiency virus type-1 （HIV-1） in China, of whom 75 000 were AIDS patients. Many AIDS patients received highly active antiretroviral therapy （HAART） supported by the ＂China CARES＂ program but the immune responses of HAART were seldom reported. This study investigated the effect of HAART on the activation and coreceptor expression of T lymphocytes in Chinese HIV/AIDS patients and evaluated its effect on immune reconstitution. Methods Seventeen HIV/AIDS patients were enrolled and three-color-flow cytometry was used to detect the activation of HLA-DR CD38 and the coreceptor CCR5, CXCR4 expression on T lymphocytes in whole blood samples taken from the patients before and after 3- or 6-month HAART. Results The activation percents of CD4^＋, CD8^＋ T lymphocytes were significantly higher before therapy than the normal controls （HLA-DR/CD4： 40.47±18.85 vs 11.54±4.10; CD38/CD4： 81.34± 10.86 vs 53.34± 11.44; HLA-DR/CD8：63.94±12.71 vs 25.67±9.18; CD38/CD8： 86.56± 11.41 vs 58.84±6.16,. all P〈0.01）. After 6-month combined antiretroviral treatment, the activation of T lymphocytes in HIV/AIDS patients was significantly decreased （HLA-DR/CD4：28.31± 13.48; CD38/CD4：69.88 ± 12.64; HLA-DR/CD8： 46.56± 18.64; CD38/CD8： 70.17±14.54, all P〈0.01 compared with the pre-treatment values）. Before the treatment, CCR5 expression on CD8^＋ T lymphocytes was up-regulated while CXCR4 expression on CD8^＋ T lymphocytes downregulated in HIV/AIDS patients compared with the normal controls （CD8/CCR5：70.91 ± 10.03 vs 52.70± 7.68; CD8/CXCR4：24.14±11.08 vs 50.05±11.68, all P〈0.01）. After 6-month HAART, CCR5 expression on CD8^＋ T lymphocytes significantly decreased （56.35±2.96, P〈0.01）, while CXCR4 expression on CD8^＋ T lymphocytes increased （36.95±9.96, P〈0.05） compared with the pre-treatment and the normal controls. A significant statistical relationship was observed between the expression of ac展开更多
Background The frequencies of regulatory T cells （Tregs） increased over the HIV infection but its counts actually decreased. We proposed that the decrease of Treg counts may cause the reduction of inhibitory effect ...Background The frequencies of regulatory T cells （Tregs） increased over the HIV infection but its counts actually decreased. We proposed that the decrease of Treg counts may cause the reduction of inhibitory effect and thereby account for the over-activation of Tregs during HIV infection. However, it remains unknown whether Tregs are also over-activated and thereafter the activation induced death may lead to the decrease of Tregs. Methods Tregs were defined as CD4＋CD25＋CD127lo/-T cells. Eighty-one HIV-1 infected patients were enrolled in our study, and twenty-two HIV-1 seronegative donors were recruited as the control. The levels of HLA-DR on Tregs were determined by FACSAria flow cytometer. Results Compared to HIV-1 seronegative donors, the levels of HLA-DR on CD4＋CD25＋CD127lo/- Tregs were significantly increased in HIV-1 infected patients, and its increase was positively associated with viral loads （r=0.3163, P=-0.004） and negatively with CD4 T-cell counts （r=-0.4153, P 〈0.0001）. In addition, significant associations between HLA-DR expression on CD4＋CD25＋CD127lo/- Tregs and the percentages of HLA-DR, CD38, Ki67 expressing CD4＋ and CD8＋ T cells were also identified. Conclusion HLA-DR on Tregs is a good marker for viral replication and disease progression. The over-activation of Tregs might result in the decrease of Tregs.展开更多
Upon encountering the antigen (Ag), the immune system can either develop a specific immune response or enter a specific state of unresponsiveness, tolerance. The response of B cells to their specific Ag can be activat...Upon encountering the antigen (Ag), the immune system can either develop a specific immune response or enter a specific state of unresponsiveness, tolerance. The response of B cells to their specific Ag can be activation and proliferation, leading to the immune response, or anergy and activation-induced cell death (AICD), leading to tolerance. AICD in B lymphocytes is a highly regulated event initiated by crosslinking of the B cell receptor (BCR). BCR engagement initiates several signaling events such as activation of PLCr, Ras, and PI3K, which generally speaking, lead to survival. However, in the absence of survival signals (CD40 or IL-4R engagement), BCR crosslinking can also promote apoptotic signal transduction pathways such as activation of effector caspases, expression of pro-apoptotic genes, and inhibition of pro-survival genes. The complex interplay between survival and death signals determines the B cell fate and, consequently, the immune response.展开更多
Cold-inducible RNA-binding protein (CIRP) is a novel inflammatory mediator that stimulates the release of proinflammatory cytokines from macrophages in sepsis. Given the immune dysregulation that characterizes sepsis,...Cold-inducible RNA-binding protein (CIRP) is a novel inflammatory mediator that stimulates the release of proinflammatory cytokines from macrophages in sepsis. Given the immune dysregulation that characterizes sepsis, the effect of CIRP on other immune cells is an area of increasing interest that has not yet been studied. In the present study, we hypothesized that extracellular CIRP promotes activation of T lymphocytes in the spleen during sepsis. We observed that mice subjected to sepsis by cecal ligation and puncture showed significantly higher expression of the early activation markers CD69 and CD25 at 20 h on CD4+ splenic T cells, and significantly higher CD69 expression on CD8+ splenic T cells compared with sham-operated controls. Furthermore, at 20 h after receiving intravenous injection of recombinant murine CIRP (rmCIRP, 5 mg/kg body weight (BW)) or PBS (vehicle), those mice receiving rmCIRP showed significantly increased expression of CD69 and CD25 on both CD4+ and CD8+ splenic T cells. This effect, however, was not seen in TLR4-deficient mice after rmCIRP injection. In addition, treatment with CIRP predisposed CD4+ T cells to a Th1 hyperinflammatory response profile, and influenced CD8+ T cells toward a cytotoxic profile. Taken together, our findings indicate that CIRP is a proinflammatory mediator that plays an important role in T-cell dysregulation during sepsis in a TLR4-dependent manner.展开更多
Objective: Despite the existence of several therapeutic strategies, the management of cervical cancer remains challenging. Our region has very little data on the interaction between the immune system and the clinical ...Objective: Despite the existence of several therapeutic strategies, the management of cervical cancer remains challenging. Our region has very little data on the interaction between the immune system and the clinical response to chemotherapy. This work examines plasma levels of galectin-3 (Gal-3) and percentages of activated T cells in patients with cervical cancer treated with chemotherapy and investigates if there is a relationship between the rates of these two elements. Methods: We compared data from 37 patients with cervical cancer undergoing chemotherapy and 42 controls with normal cervical cytology. Plasma Gal-3 concentrations were assessed by ELISA and expression of activation markers by T cells (CD69 and HLA-DR) was assessed by flow cytometry at three different time points during chemotherapy. Results: Our results showed that patients had a significantly higher concentration of Gal-3 compared to controls (4.025 vs. 1.340, p 0.001), similarly, they had a significantly high percentage of activated lymphocytes (2.610 vs. 0.731;p 0.0001). According to the response to treatment, patients with no response to treatment had a lower concentration of circulating Gal-3 but had approximately the same percentage of activated CD4 and CD8 lymphocytes as patients with a partial or total response. In addition, we found a positive correlation between the Gal-3 level and CD4 T cells expressing the activation marker CD69 (p 0.05;rho = 0.44). Conclusion: In conclusion, our results show that there would be a relationship between circulating galectin-3 and the percentage of peripheral CD4+</sup>CD69+</sup> cells in cervical cancer.展开更多
目的应用中药血清药理学的方法，通过时间一效应关系研究，探讨大补阴丸（汤）含药血清对CJ（Campylobacter jejuni，空肠弯曲菌）致敏的自身免疫病模型小鼠（CJ小鼠）T、B淋巴细胞活性的影响及其时间-效应关系。方法将健康雌性ICR小鼠...目的应用中药血清药理学的方法，通过时间一效应关系研究，探讨大补阴丸（汤）含药血清对CJ（Campylobacter jejuni，空肠弯曲菌）致敏的自身免疫病模型小鼠（CJ小鼠）T、B淋巴细胞活性的影响及其时间-效应关系。方法将健康雌性ICR小鼠随机分为正常对照组（normalcontrolgroup，N）、模型组（modelgroup，M）、模型对照组（model control group，MC）以及5个时相给药组（30min、1h、1．5h、2h、3h），共8组。除正常对照组外，其他各组均用空肠弯曲菌免疫小鼠制备自身免疫病模型。从造模第15d起，开始以大补阴丸（汤）（0．4g生药饮片／ml）给不同时相用药组小鼠灌胃，连续用药10d。并分别于第10次给药后30min、1h、1．5h、2h、3h取血，分离血清；同时也分别取N组、MC组血，分离血清。继之处死小鼠，称量脾，计算脾指数。将上述血清与M组小鼠的脾细胞体外培养。检测DBYW含药血清对T、B淋巴细胞活性的影响，并绘出时-效关系变化曲线。结果大补阴丸（汤）在1～1．5h时相含药血清，可明显抑制CJ小鼠的T、B淋巴细胞增殖活性，降低CJ小鼠体内异常升高的ds-DNA、ss-DNA抗体水平和脾指数，改善其因自身免疫反应所致的肝肾病理损害。结论大补阴丸（汤）含药血清对异常免疫机能状态下的T、B淋巴细胞活性具有明显的免疫抑制作用，且在1～1．5h时作用最明显。展开更多
基金This research was supported by the grants from the "Tenth Five-Year" Plan on Tackling Key Problems of National Science and Technology of PRC (No. 2004BA719A12), the Project of Medical Innovation of Liaoning Province (No. [2004]37), and the Fund of Centre for Doctors of Ministry of Education (No. 20040159005).
文摘Background At the end of 2005, 650 000 people lived with human immunodeficiency virus type-1 （HIV-1） in China, of whom 75 000 were AIDS patients. Many AIDS patients received highly active antiretroviral therapy （HAART） supported by the ＂China CARES＂ program but the immune responses of HAART were seldom reported. This study investigated the effect of HAART on the activation and coreceptor expression of T lymphocytes in Chinese HIV/AIDS patients and evaluated its effect on immune reconstitution. Methods Seventeen HIV/AIDS patients were enrolled and three-color-flow cytometry was used to detect the activation of HLA-DR CD38 and the coreceptor CCR5, CXCR4 expression on T lymphocytes in whole blood samples taken from the patients before and after 3- or 6-month HAART. Results The activation percents of CD4^＋, CD8^＋ T lymphocytes were significantly higher before therapy than the normal controls （HLA-DR/CD4： 40.47±18.85 vs 11.54±4.10; CD38/CD4： 81.34± 10.86 vs 53.34± 11.44; HLA-DR/CD8：63.94±12.71 vs 25.67±9.18; CD38/CD8： 86.56± 11.41 vs 58.84±6.16,. all P〈0.01）. After 6-month combined antiretroviral treatment, the activation of T lymphocytes in HIV/AIDS patients was significantly decreased （HLA-DR/CD4：28.31± 13.48; CD38/CD4：69.88 ± 12.64; HLA-DR/CD8： 46.56± 18.64; CD38/CD8： 70.17±14.54, all P〈0.01 compared with the pre-treatment values）. Before the treatment, CCR5 expression on CD8^＋ T lymphocytes was up-regulated while CXCR4 expression on CD8^＋ T lymphocytes downregulated in HIV/AIDS patients compared with the normal controls （CD8/CCR5：70.91 ± 10.03 vs 52.70± 7.68; CD8/CXCR4：24.14±11.08 vs 50.05±11.68, all P〈0.01）. After 6-month HAART, CCR5 expression on CD8^＋ T lymphocytes significantly decreased （56.35±2.96, P〈0.01）, while CXCR4 expression on CD8^＋ T lymphocytes increased （36.95±9.96, P〈0.05） compared with the pre-treatment and the normal controls. A significant statistical relationship was observed between the expression of ac
文摘Background The frequencies of regulatory T cells （Tregs） increased over the HIV infection but its counts actually decreased. We proposed that the decrease of Treg counts may cause the reduction of inhibitory effect and thereby account for the over-activation of Tregs during HIV infection. However, it remains unknown whether Tregs are also over-activated and thereafter the activation induced death may lead to the decrease of Tregs. Methods Tregs were defined as CD4＋CD25＋CD127lo/-T cells. Eighty-one HIV-1 infected patients were enrolled in our study, and twenty-two HIV-1 seronegative donors were recruited as the control. The levels of HLA-DR on Tregs were determined by FACSAria flow cytometer. Results Compared to HIV-1 seronegative donors, the levels of HLA-DR on CD4＋CD25＋CD127lo/- Tregs were significantly increased in HIV-1 infected patients, and its increase was positively associated with viral loads （r=0.3163, P=-0.004） and negatively with CD4 T-cell counts （r=-0.4153, P 〈0.0001）. In addition, significant associations between HLA-DR expression on CD4＋CD25＋CD127lo/- Tregs and the percentages of HLA-DR, CD38, Ki67 expressing CD4＋ and CD8＋ T cells were also identified. Conclusion HLA-DR on Tregs is a good marker for viral replication and disease progression. The over-activation of Tregs might result in the decrease of Tregs.
文摘Upon encountering the antigen (Ag), the immune system can either develop a specific immune response or enter a specific state of unresponsiveness, tolerance. The response of B cells to their specific Ag can be activation and proliferation, leading to the immune response, or anergy and activation-induced cell death (AICD), leading to tolerance. AICD in B lymphocytes is a highly regulated event initiated by crosslinking of the B cell receptor (BCR). BCR engagement initiates several signaling events such as activation of PLCr, Ras, and PI3K, which generally speaking, lead to survival. However, in the absence of survival signals (CD40 or IL-4R engagement), BCR crosslinking can also promote apoptotic signal transduction pathways such as activation of effector caspases, expression of pro-apoptotic genes, and inhibition of pro-survival genes. The complex interplay between survival and death signals determines the B cell fate and, consequently, the immune response.
基金We thank Dr Kevin Tracey for providing the Tlr4−/−mice and the members of the Flow Cytometry Core Facility at the Feinstein Institute for Medical Research for their input and technical assistanceThis study was supported by the National Institutes of Health(NIH)Grants HL076179 and GM053008(PW).
文摘Cold-inducible RNA-binding protein (CIRP) is a novel inflammatory mediator that stimulates the release of proinflammatory cytokines from macrophages in sepsis. Given the immune dysregulation that characterizes sepsis, the effect of CIRP on other immune cells is an area of increasing interest that has not yet been studied. In the present study, we hypothesized that extracellular CIRP promotes activation of T lymphocytes in the spleen during sepsis. We observed that mice subjected to sepsis by cecal ligation and puncture showed significantly higher expression of the early activation markers CD69 and CD25 at 20 h on CD4+ splenic T cells, and significantly higher CD69 expression on CD8+ splenic T cells compared with sham-operated controls. Furthermore, at 20 h after receiving intravenous injection of recombinant murine CIRP (rmCIRP, 5 mg/kg body weight (BW)) or PBS (vehicle), those mice receiving rmCIRP showed significantly increased expression of CD69 and CD25 on both CD4+ and CD8+ splenic T cells. This effect, however, was not seen in TLR4-deficient mice after rmCIRP injection. In addition, treatment with CIRP predisposed CD4+ T cells to a Th1 hyperinflammatory response profile, and influenced CD8+ T cells toward a cytotoxic profile. Taken together, our findings indicate that CIRP is a proinflammatory mediator that plays an important role in T-cell dysregulation during sepsis in a TLR4-dependent manner.
文摘Objective: Despite the existence of several therapeutic strategies, the management of cervical cancer remains challenging. Our region has very little data on the interaction between the immune system and the clinical response to chemotherapy. This work examines plasma levels of galectin-3 (Gal-3) and percentages of activated T cells in patients with cervical cancer treated with chemotherapy and investigates if there is a relationship between the rates of these two elements. Methods: We compared data from 37 patients with cervical cancer undergoing chemotherapy and 42 controls with normal cervical cytology. Plasma Gal-3 concentrations were assessed by ELISA and expression of activation markers by T cells (CD69 and HLA-DR) was assessed by flow cytometry at three different time points during chemotherapy. Results: Our results showed that patients had a significantly higher concentration of Gal-3 compared to controls (4.025 vs. 1.340, p 0.001), similarly, they had a significantly high percentage of activated lymphocytes (2.610 vs. 0.731;p 0.0001). According to the response to treatment, patients with no response to treatment had a lower concentration of circulating Gal-3 but had approximately the same percentage of activated CD4 and CD8 lymphocytes as patients with a partial or total response. In addition, we found a positive correlation between the Gal-3 level and CD4 T cells expressing the activation marker CD69 (p 0.05;rho = 0.44). Conclusion: In conclusion, our results show that there would be a relationship between circulating galectin-3 and the percentage of peripheral CD4+</sup>CD69+</sup> cells in cervical cancer.
文摘目的应用中药血清药理学的方法，通过时间一效应关系研究，探讨大补阴丸（汤）含药血清对CJ（Campylobacter jejuni，空肠弯曲菌）致敏的自身免疫病模型小鼠（CJ小鼠）T、B淋巴细胞活性的影响及其时间-效应关系。方法将健康雌性ICR小鼠随机分为正常对照组（normalcontrolgroup，N）、模型组（modelgroup，M）、模型对照组（model control group，MC）以及5个时相给药组（30min、1h、1．5h、2h、3h），共8组。除正常对照组外，其他各组均用空肠弯曲菌免疫小鼠制备自身免疫病模型。从造模第15d起，开始以大补阴丸（汤）（0．4g生药饮片／ml）给不同时相用药组小鼠灌胃，连续用药10d。并分别于第10次给药后30min、1h、1．5h、2h、3h取血，分离血清；同时也分别取N组、MC组血，分离血清。继之处死小鼠，称量脾，计算脾指数。将上述血清与M组小鼠的脾细胞体外培养。检测DBYW含药血清对T、B淋巴细胞活性的影响，并绘出时-效关系变化曲线。结果大补阴丸（汤）在1～1．5h时相含药血清，可明显抑制CJ小鼠的T、B淋巴细胞增殖活性，降低CJ小鼠体内异常升高的ds-DNA、ss-DNA抗体水平和脾指数，改善其因自身免疫反应所致的肝肾病理损害。结论大补阴丸（汤）含药血清对异常免疫机能状态下的T、B淋巴细胞活性具有明显的免疫抑制作用，且在1～1．5h时作用最明显。
