BACKGROUND:Human CD8 + CD28 - T-suppressor(Ts) cells have been considered to indicate a reduced need for immunosuppression in pediatric liver-intestine transplant recipients and recipients of deceased heart-kidney tra...BACKGROUND:Human CD8 + CD28 - T-suppressor(Ts) cells have been considered to indicate a reduced need for immunosuppression in pediatric liver-intestine transplant recipients and recipients of deceased heart-kidney transplants.However,in adult-to-adult living donor liver transplantation(A-A LDLT)little information is available and the clinical significance is still unknown. METHODS:Flow cytometry was used to detect the population of CD8+CD28 -Ts cells present in peripheral blood in A-A LDLT recipients(n=31),patients with end- stage liver disease(n=24)and healthy controls(n=19). Meanwhile,we tested the graft function and trough levels of immunosuppression in recipients.The clinical and follow- up data of 31 transplant recipients were analyzed. RESULTS:Compared with diseased controls(P=0.007) and healthy individuals(P=0.000),a notable expansion of CD8 + CD28 - Ts cells was found in recipients of A-A LDLT.This was associated with graft function,levels of immunosuppression and rejection episodes. CONCLUSIONS:To monitor the CD8 + CD28 - Ts cells levels is important to evaluate the immune state of recipients. Meanwhile,it is also important to promote expansion of CD8+CD28 -Ts cells in recipients of A-A LDLT,not only to sustain good graft function and decrease the dosage of immunosuppressants,but also to reduce the occurrence of rejection.展开更多
Myeloid-derived suppressor cells （MDSCs） play a crucial role in T cell dysfunction, which is related to poor outcome in patients with severe trauma. Cyclooxygenase-2 （Cox-2） contributes to immune disorder in traum...Myeloid-derived suppressor cells （MDSCs） play a crucial role in T cell dysfunction, which is related to poor outcome in patients with severe trauma. Cyclooxygenase-2 （Cox-2） contributes to immune disorder in trauma and infection via production of prostaglandin E2. However, the role of Cox-2 in the accumulation and function of MDSCs after traumatic stress has not been fully elucidated. In the present study, we treated murine trauma model with NS398, a selective Cox-2 inhibitor. Then the percentages of CD1 lb＋/Gr-l＋ cells, proliferation and apoptosis of CD4＋ T cells were determined. Ar- ginase activity and arginase-1 （Arg-1） protein expression of splenic CDllb＋/Gr-I＋ cells, and de- layed-type hypersensitivity （DTH） response were analyzed. The results showed that Cox-2 blockade significantly decreased the percentages of CD1 lb＋/Gr-l＋ cells in the spleen and bone marrow 48 and 72 h after traumatic stress. NS398 inhibited arginase activity and down-regulated the Arg-1 expression of splenic CD1 lb＋/Gr-l＋ ceils. Moreover, NS398 could promote proliferation and inhibit apoptosis of CD4＋ T cells. It also restored DTH response of traumatic mice. Taken together, our data revealed that Cox-2 might play a pivotal role in the accumulation and function of MDSC after traumatic stress.展开更多
Susceptibility to infection in patients with obstructive jaundice is much more higher than non-jaundiced patients. The reasons for this are not completely understood. It is postulated that this may have some relation ...Susceptibility to infection in patients with obstructive jaundice is much more higher than non-jaundiced patients. The reasons for this are not completely understood. It is postulated that this may have some relation to changes of patients′immune function. This article reported the changes of splenocyte IL-2 production and T Suppressor cell activity in rats with obstructive jaundice. Meanwhile, we also investigated effects of cimetidine on immune function in rats with bile duct ligation. The results show that IL-2 production in obstructive jaundiced rats significantly decreased and T suppressor cell activity markably increased. Cimetidine could remarkably enhance IL-2 production and suppress T Suppressor cell activity. Abmormaility of immune function may be one reason for high susceptibility to infection in patients with obstructive jaundice in perioperative period. Cimetidine, which could clearly improve immune function in rats with obstructive jaundice, might be a valuable agent for strengthening the capacity of fighting infection in patients with obstructive jaundice.展开更多
目的分析T细胞活化免疫球蛋白抑制V型结构域(V-domain Ig suppressor of T cell activation,VISTA)在幼年特发性关节炎(juvenile idiopathic arthritis,JIA)患儿外周血的表达情况,探讨其在发病中的作用。方法前瞻性收集不同亚型JIA患儿...目的分析T细胞活化免疫球蛋白抑制V型结构域(V-domain Ig suppressor of T cell activation,VISTA)在幼年特发性关节炎(juvenile idiopathic arthritis,JIA)患儿外周血的表达情况,探讨其在发病中的作用。方法前瞻性收集不同亚型JIA患儿(47例)及健康儿童(10例)的外周血,利用流式细胞术检测CD14+单核细胞、CD4+T淋巴细胞、CD8+T淋巴细胞上VISTA、干扰素-γ(interfern-γ,IFN-γ)、肿瘤坏死因子-α(tumor necrosis factor-α,TNF-α)的表达情况。结果VISTA在JIA患儿中的表达水平比健康儿童低(P<0.05);不同亚型JIA患儿VISTA表达差异有统计学意义,以全身型表达水平最低(P<0.05);不同免疫细胞表达VISTA差异有统计学意义,单核细胞表面VISTA表达水平更高(P<0.05)。相关性分析发现CD4+T细胞上VISTA与IFN-γ(r=-0.436,P<0.05)、TNF-α(r=-0.382,P<0.05)表达呈负相关,CD8+T细胞上VISTA与IFN-γ(r=-0.348,P<0.05)、TNF-α(r=-0.487,P<0.05)表达呈负相关;CD14+单核细胞上VISTA与IFN-γ(r=-0.582,P<0.05)、TNF-α(r=-0.603,P<0.05)表达呈负相关。结论VISTA表达不足可能与JIA发病相关,增强VISTA的免疫调节作用可能是未来治疗JIA的途径之一。展开更多
In this report,a comparative study is made of the function test of spontaneousT suppressor cell（STs）and T Lymphocyte subsets in patients with epidemic hemorrha-gic fever（EHF）.It was found that in the early stages ...In this report,a comparative study is made of the function test of spontaneousT suppressor cell（STs）and T Lymphocyte subsets in patients with epidemic hemorrha-gic fever（EHF）.It was found that in the early stages of the disease the activity of STs wasmarkedly lower than that of the controls,while the percentage of CD<sub>?</sub><sup>+</sup> cells increasedsignificantly,which led to the decrease and reciprocation of CD<sub>4</sub>/CD<sub>8</sub> ratio,and that theactivity of STs was reversely related to the proportion of CD<sub>8</sub><sup>+</sup> cells on linear regressionanalysis,indicating that the CD<sub>8</sub><sup>+</sup> cells increased may mainly belong to cytotoxic T cells.It was also shown that the changes of STs function and CD<sub>4</sub>/CD<sub>8</sub> ratio were related tothe abnormalities of serum C<sub>3</sub> content and circulating immune complex.The results sug-gest that the disturbance of host cellular immunoregulation may play an important rolein the pathogenesis of EHF.展开更多
Tumor immunity proceeds through multiple processes, which consist of antigen presentation by antigen presenting cells(APCs) to educate effector cells and destruction by the effector cytotoxic cells. However, tumor imm...Tumor immunity proceeds through multiple processes, which consist of antigen presentation by antigen presenting cells(APCs) to educate effector cells and destruction by the effector cytotoxic cells. However, tumor immunity is frequently repressed at tumor sites. Malignantly transformed cells rarely survive the attack by the immune system, but cells that do survive change their phenotypes to reduce their immunogenicity. The resultant cells evade the attack by the immune system and form clinically discernible tumors. Tumor microenvironments simultaneously contain a wide variety of immune suppressive molecules and cells to dampen tumor immunity. Moreover, the liver microenvironment exhibits immune tolerance to reduce aberrant immune responses to massively-exposed antigens via the portal vein, and immune dysfunction is frequently associated with liver cirrhosis, which is widespread in hepatocellular carcinoma(HCC) patients. Immune therapy aims to reduce tumor burden, but it is also expected to prevent non-cancerous liver lesions from progressing to HCC, because HCC develops or recurs from noncancerous liver lesions with chronic inflammatory states and/or cirrhosis and these lesions cannot be cured and/or eradicated by local and/or systemic therapies. Nevertheless, cancer immune therapy should augment specific tumor immunity by using two distinct measures: enhancing the effector cell functions such as antigen presentation capacity of APCs and tumor cell killing capacity of cytotoxic cells, and reactivating the immune system in immune-suppressive tumor microenvironments. Here, we will summarize the current status and discuss the future perspective on immune therapy for HCC.展开更多
基金supported by grants from the National Natural Science Foundation of China(No.30772124)the Doctoral Fund of the Ministry of Education of China(No.20070610147).
文摘BACKGROUND:Human CD8 + CD28 - T-suppressor(Ts) cells have been considered to indicate a reduced need for immunosuppression in pediatric liver-intestine transplant recipients and recipients of deceased heart-kidney transplants.However,in adult-to-adult living donor liver transplantation(A-A LDLT)little information is available and the clinical significance is still unknown. METHODS:Flow cytometry was used to detect the population of CD8+CD28 -Ts cells present in peripheral blood in A-A LDLT recipients(n=31),patients with end- stage liver disease(n=24)and healthy controls(n=19). Meanwhile,we tested the graft function and trough levels of immunosuppression in recipients.The clinical and follow- up data of 31 transplant recipients were analyzed. RESULTS:Compared with diseased controls(P=0.007) and healthy individuals(P=0.000),a notable expansion of CD8 + CD28 - Ts cells was found in recipients of A-A LDLT.This was associated with graft function,levels of immunosuppression and rejection episodes. CONCLUSIONS:To monitor the CD8 + CD28 - Ts cells levels is important to evaluate the immune state of recipients. Meanwhile,it is also important to promote expansion of CD8+CD28 -Ts cells in recipients of A-A LDLT,not only to sustain good graft function and decrease the dosage of immunosuppressants,but also to reduce the occurrence of rejection.
基金supported by grants from the Foundation of Science and Technology of Wuhan City(No.201161038339)Health Department of Hubei Province of China(No.QJX2010-4)+1 种基金Natural Science Foundation of Hubei Province of China(No.2011CDB205)National"Twelfth Five-Year"Plan for Science&Technology Support(No.2012BAI11B00)
文摘Myeloid-derived suppressor cells （MDSCs） play a crucial role in T cell dysfunction, which is related to poor outcome in patients with severe trauma. Cyclooxygenase-2 （Cox-2） contributes to immune disorder in trauma and infection via production of prostaglandin E2. However, the role of Cox-2 in the accumulation and function of MDSCs after traumatic stress has not been fully elucidated. In the present study, we treated murine trauma model with NS398, a selective Cox-2 inhibitor. Then the percentages of CD1 lb＋/Gr-l＋ cells, proliferation and apoptosis of CD4＋ T cells were determined. Ar- ginase activity and arginase-1 （Arg-1） protein expression of splenic CDllb＋/Gr-I＋ cells, and de- layed-type hypersensitivity （DTH） response were analyzed. The results showed that Cox-2 blockade significantly decreased the percentages of CD1 lb＋/Gr-l＋ cells in the spleen and bone marrow 48 and 72 h after traumatic stress. NS398 inhibited arginase activity and down-regulated the Arg-1 expression of splenic CD1 lb＋/Gr-l＋ ceils. Moreover, NS398 could promote proliferation and inhibit apoptosis of CD4＋ T cells. It also restored DTH response of traumatic mice. Taken together, our data revealed that Cox-2 might play a pivotal role in the accumulation and function of MDSC after traumatic stress.
文摘Susceptibility to infection in patients with obstructive jaundice is much more higher than non-jaundiced patients. The reasons for this are not completely understood. It is postulated that this may have some relation to changes of patients′immune function. This article reported the changes of splenocyte IL-2 production and T Suppressor cell activity in rats with obstructive jaundice. Meanwhile, we also investigated effects of cimetidine on immune function in rats with bile duct ligation. The results show that IL-2 production in obstructive jaundiced rats significantly decreased and T suppressor cell activity markably increased. Cimetidine could remarkably enhance IL-2 production and suppress T Suppressor cell activity. Abmormaility of immune function may be one reason for high susceptibility to infection in patients with obstructive jaundice in perioperative period. Cimetidine, which could clearly improve immune function in rats with obstructive jaundice, might be a valuable agent for strengthening the capacity of fighting infection in patients with obstructive jaundice.
文摘In this report,a comparative study is made of the function test of spontaneousT suppressor cell（STs）and T Lymphocyte subsets in patients with epidemic hemorrha-gic fever（EHF）.It was found that in the early stages of the disease the activity of STs wasmarkedly lower than that of the controls,while the percentage of CD<sub>?</sub><sup>+</sup> cells increasedsignificantly,which led to the decrease and reciprocation of CD<sub>4</sub>/CD<sub>8</sub> ratio,and that theactivity of STs was reversely related to the proportion of CD<sub>8</sub><sup>+</sup> cells on linear regressionanalysis,indicating that the CD<sub>8</sub><sup>+</sup> cells increased may mainly belong to cytotoxic T cells.It was also shown that the changes of STs function and CD<sub>4</sub>/CD<sub>8</sub> ratio were related tothe abnormalities of serum C<sub>3</sub> content and circulating immune complex.The results sug-gest that the disturbance of host cellular immunoregulation may play an important rolein the pathogenesis of EHF.
基金Supported by(in part)Research Programs on the Innovative Development and Application for New Drugs for Hepatitis B(No.17fk0310116h0001) from the Japan Agency for Medical Research and Development(AMED)Extramural Collaborative Research Grant of Cancer Research Institute,Kanazawa University
文摘Tumor immunity proceeds through multiple processes, which consist of antigen presentation by antigen presenting cells(APCs) to educate effector cells and destruction by the effector cytotoxic cells. However, tumor immunity is frequently repressed at tumor sites. Malignantly transformed cells rarely survive the attack by the immune system, but cells that do survive change their phenotypes to reduce their immunogenicity. The resultant cells evade the attack by the immune system and form clinically discernible tumors. Tumor microenvironments simultaneously contain a wide variety of immune suppressive molecules and cells to dampen tumor immunity. Moreover, the liver microenvironment exhibits immune tolerance to reduce aberrant immune responses to massively-exposed antigens via the portal vein, and immune dysfunction is frequently associated with liver cirrhosis, which is widespread in hepatocellular carcinoma(HCC) patients. Immune therapy aims to reduce tumor burden, but it is also expected to prevent non-cancerous liver lesions from progressing to HCC, because HCC develops or recurs from noncancerous liver lesions with chronic inflammatory states and/or cirrhosis and these lesions cannot be cured and/or eradicated by local and/or systemic therapies. Nevertheless, cancer immune therapy should augment specific tumor immunity by using two distinct measures: enhancing the effector cell functions such as antigen presentation capacity of APCs and tumor cell killing capacity of cytotoxic cells, and reactivating the immune system in immune-suppressive tumor microenvironments. Here, we will summarize the current status and discuss the future perspective on immune therapy for HCC.
