Background:Visceral adipose tissue(VAT)has been linked to the severe acute pancreatitis(SAP)prognosis,although the underlying mechanism remains unclear.It has been reported that pyroptosis worsens SAP.The present stud...Background:Visceral adipose tissue(VAT)has been linked to the severe acute pancreatitis(SAP)prognosis,although the underlying mechanism remains unclear.It has been reported that pyroptosis worsens SAP.The present study aimed to verify whether mesenteric adipose tissue(MAT,a component of VAT)can cause secondary intestinal injury through the pyroptotic pathway.Methods:Thirty-six male Sprague Dawley(SD)rats were divided into six different groups.Twelve rats were randomly divided into the SAP and control groups.We monitored the changes of MAT and B lymphocytes infiltration in MAT of SAP rats.Twelve SAP rats were injected with MAT B lymphocytes or phosphate buffer solution(PBS).The remaining twelve SAP rats were first injected with MAT B lymphocytes,and then with MCC950(NLRP3 inhibitor)or PBS.We collected blood and tissue samples from pancreas,gut and MAT for analysis.Results:Compared to the control rats,the SAP group showed inflammation in MAT,including higher expression of tumor necrosis factor(TNF-α)and interleukin-6(IL-6),lower expression of IL-10,and histological changes.Flow cytometry analysis revealed B lymphocytes infiltration in MAT but not T lymphocytes and macrophages.The SAP rats also exhibited intestinal injury,characterized by lower expression of zonula occludens-1(ZO-1)and occludin,higher levels of lipopolysaccharide and diamine oxidase,and pathological changes.The expression of NLRP3 and n-GSDMD,which are responsible for pyroptosis,was increased in the intestine of SAP rats.The injection of MAT B lymphocytes into SAP rats exacerbated the inflammation in MAT.The upregulation of pyroptosis reduced tight junction in the intestine,which contributed to the SAP progression,including higher inflammatory indicators and worse histological changes.The administration of MCC950 to SAP+MAT B rats downregulated pyroptosis,which subsequently improved the intestinal barrier and ameliorated inflammatory response of SAP.Conclusions:In SAP,MAT B lymphocytes aggravated local inflammation,and promoted the injury to the intestine through the enteric pyroptotic pathway.展开更多
As the average age of the world population increases,more people will face debilitating aging-associated conditions,including dementia and stroke.Not only does the incidence of these conditions increase with age,but t...As the average age of the world population increases,more people will face debilitating aging-associated conditions,including dementia and stroke.Not only does the incidence of these conditions increase with age,but the recovery afterward is often worse in older patients.Researchers and health professionals must unveil and understand the factors behind age-associated diseases to develop a therapy for older patients.Aging causes profound changes in the immune system including the activation of microglia in the brain.Activated microglia promote T lymphocyte transmigration leading to an increase in neuroinflammation,white matter damage,and cognitive impairment in both older humans and rodents.The presence of T and B lymphocytes is observed in the aged brain and correlates with worse stroke outcomes.Preclinical strategies in stroke target either microglia or the lymphocytes or the communications between them to promote functional recovery in aged subjects.In this review,we examine the role of the microglia and T and B lymphocytes in aging and how they contribute to cognitive impairment.Additionally,we provide an important update on the contribution of these cells and their interactions in preclinical aged stroke.展开更多
Objective:This study aimed to compare the efficacy of anti-CD19 chimeric antigen receptor T cells(CAR-T cells)versus chemotherapy plus donor lymphocyte infusion(chemo-DLI)for treating relapsed CD 19-positive B-cell ac...Objective:This study aimed to compare the efficacy of anti-CD19 chimeric antigen receptor T cells(CAR-T cells)versus chemotherapy plus donor lymphocyte infusion(chemo-DLI)for treating relapsed CD 19-positive B-cell acute lymphoblastic leukemia(B-ALL)after allogeneic hematopoietic stem cell transplantation(allo-HSCT).Methods:Clinical data of 43 patients with B-ALL who relapsed after allo-HSCT were retrospectively analyzed.Twenty-two patients were treated with CAR-T cells(CAR-T group),and 21 with chemotherapy plus DLI(chemo-DLI group).The complete remission(CR)and minimal residual disease(MRD)-negative CR rates,leukemia-free survival(LFS)rate,overall survival(OS)rate,and incidence of acute graft-versus-host disease(aGVHD),cytokine release syndrome(CRS)and immune effector cell-associated neurotoxicity syndrome(ICANS)were compared between the two groups.Results:The CR and MRD-negative CR rates in the CAR-T group(77.3%and 61.5%)were significantly higher than those in the chemo-DLI group(38.1%and 23.8%)(P=0.008 and P=0.003).The 1-and 2-year LFS rates in the CAR-T group were superior to those in the chemo-DLI group:54.5%and 50.0%vs.9.5%and 4.8%(P=0.0001 and P=0.00004).The 1-and 2-year OS rates in the CAR-T versus chemo-DLI group were 59.1%and 54.5%vs.19%and 9.5%(P=0.011 and P=0.003).Six patients(28.6%)with grade 2-4 aGVHD were identified in the chemo-DLI group.Two patients(9.1%)in the CAR-T group developed grade 1-2 aGVHD.Nineteen patients(86.4%)developed CRS in the CAR-T group,comprising grade 1-2 CRS in 13 patients(59.1%)and grade 3 CRS in 6 patients(27.3%).Two patients(9.1%)developed grade 1-2 ICANS.Conclusion:Donor-derived anti-CD19 CAR-T-cell therapy may be better,safer,and more effective than chemo-DLI for B-ALL patients who relapse after allo-HSCT.展开更多
Bone remodeling is a tightly regulated resorption and formation of bone matrix for physiological processes or to maintain bone function. Bone remodeling involves the synchronized differentiation and activity of bone-r...Bone remodeling is a tightly regulated resorption and formation of bone matrix for physiological processes or to maintain bone function. Bone remodeling involves the synchronized differentiation and activity of bone-related cell types including bone matrix-depositing osteoblasts, bone matrix-resorbing osteoclasts, collagen/extracellular matrix-producing chondrocytes, and the progenitors of these cell types. T and B cells are adaptive immune cells that can influence bone remodeling by directly regulating the function of bone-related cells under normal and pathophysiological conditions. The specific mechanisms through which T cells control remodeling are not well defined. Here, we review the impact and influence of T cells and their products on the differentiation and function of bone cells during bone remodeling. Synthesizing new connections and highlighting potential mechanisms may promote additional avenues of study to elucidate the full role that immune cells play in regulating bone homeostasis.展开更多
Background:Colorectal cancer(CRC)is a common gastrointestinal malignancy.The T lymphocyte subsets are important in the develop-ment,invasion and metastasis of tumors,including CRC.Nevertheless,limited research has exp...Background:Colorectal cancer(CRC)is a common gastrointestinal malignancy.The T lymphocyte subsets are important in the develop-ment,invasion and metastasis of tumors,including CRC.Nevertheless,limited research has explored the relationship between T cell subpopu-lations and the clinical characteristics of CRC.This study compared the T lymphocyte subsets in patients with CRC and healthy individuals,and assessed the relationship between these values and clinical characteristics.Methods:Peripheral blood was collected from 100 patients with CRC and 54 healthy individuals.The numbers of CD3^(+)T,CD4^(+)T,and CD8^(+)T lymphocytes,NK cells,and the CD4^(+)T/CD8^(+)T ratio in peripheral blood were measured using flow cytometry,and were compared between CRC patients and healthy individuals.Spearman's correlation analysis was performed to investigate the relationship between the T lymphocyte subsets in patients diagnosed with CRC and the levels of carcinoembryonic antigen(CEA)and thymidine kinase 1(TK1).Receiver operating characteristic(ROC)curves were utilized to evaluate the potential utility of the T lymphocyte counts in predicting lymph node metastasis,vas-cular infiltration,and high Ki-67 expression.Results:The CRC patients had lower counts of CD3^(+)T,CD4^(+)T,and CD8^(+)T lymphocytes compared to the healthy population(P<0.05).However,no significant differences were observed in the CD4^(+)/CD8^(+)ratio or NK cells(P>0.05).Notably,the CD3^(+)T,CD4^(+)T,and CD8^(+)T lym-phocyte counts were higher in patients with stageⅠ-Ⅱdisease,no lymph node metastasis,no vascular invasion,and low Ki-67 expression than in those with stageⅢ,lymph node metastasis,vascular invasion,and high Ki-67 expression(P<0.05).There was a negative association be-tween the CD3^(+)T,CD4^(+)T,and CD8^(+)T lymphocyte counts and CEA and TK1 levels in patients with CRC.The ROC curves demonstrated that CD3^(+)T,CD4^(+)T,and CD8^(+)T lymphocyte counts had significant predictive value for lymph node metastasis,vascular infiltration,and high Ki-67 expression.Conclusions:The peripheral blood CD3^(+)T,CD4^(+)T,and CD8^(+)T lymphocyte counts are related to the clinical traits of patients with CRC and can predict the prognosis of the disease.展开更多
旨在通过免疫信息学方法预测非洲猪瘟病毒(ASFV)结构蛋白的T、B细胞表位,为非洲猪瘟(ASF)表位疫苗的设计研制提供参考。从NCBI和RCSB数据库获取ASFV蛋白质序列和三维结构,利用IEDB、DTU Health Tech等数据库的生物信息学工具对ASFV的5...旨在通过免疫信息学方法预测非洲猪瘟病毒(ASFV)结构蛋白的T、B细胞表位,为非洲猪瘟(ASF)表位疫苗的设计研制提供参考。从NCBI和RCSB数据库获取ASFV蛋白质序列和三维结构,利用IEDB、DTU Health Tech等数据库的生物信息学工具对ASFV的5种结构蛋白p72、p17、p49、M1249L和H240R的细胞毒性T细胞表位、线性B细胞和构象B细胞表位进行鉴定。结果显示:5种蛋白质均为亲水性,二级结构以无规则卷曲为主,仅M1249L例外;预测到抗原性良好、无毒、无致敏的细胞毒性T细胞优势表位27个,线性B细胞优势表位35个;预测到仅针对p72的构象B细胞优势表位2个。结论:ASFV的5种蛋白质可能具有多个潜在T、B细胞表位,其中B细胞表位相对占优,5种蛋白质中p72和M1249L最具疫苗研发前景,可结合蛋白质相关参数信息为构建ASF表位疫苗提供参考。展开更多
背景乙型肝炎病毒(hepatitis B virus,HBV)相关慢性肝病患者外周血T细胞及细胞因子水平与患者免疫功能状态密切相关,不同疾病程度的HBV相关肝病患者的T细胞、细胞因子水平及与肝病阶段的相关性值得进一步探究.目的探究不同阶段HBV相关...背景乙型肝炎病毒(hepatitis B virus,HBV)相关慢性肝病患者外周血T细胞及细胞因子水平与患者免疫功能状态密切相关,不同疾病程度的HBV相关肝病患者的T细胞、细胞因子水平及与肝病阶段的相关性值得进一步探究.目的探究不同阶段HBV相关慢性肝病患者外周血T细胞亚群计数、细胞因子变化特点及关联性.方法本研究为一项观察性研究,共纳入慢性乙型肝炎(chronic hepatitis B,CHB)患者65例,肝硬化失代偿期(decompensated cirrhosis,DCC)患者122例,肝细胞癌(hepatocellular carcinoma,HCC)患者109例,收集患者一般信息、病史、治疗情况及实验室检查结果、Child-Paugh分级及HCC患者肿瘤巴塞罗那分期,分析各项指标,尤其是T细胞亚群计数及细胞因子的组间差异及特征.结果HBV相关肝硬化、HCC患者外周血CD8^(+)T细胞水平与Child分级A到C呈负相关.HCC患者CD8^(+)T细胞绝对计数显著低于DCC[240(150-379)cells/μLvs 277(154-435)cells/μL,P<0.05]及CHB[240(150-379)cells/μL vs 452(269-706)cells/μL,P<0.001]患者.白细胞介素(interleukin,IL)-6、IL-8、肿瘤坏死因子(tumor necrosis factor,TNF)-α在HCC组均最高.DCC、HCC患者Child-Paugh分级越差,CD3^(+)、CD8^(+)T细胞水平越低,IL-6水平越高.HCC患者CD3^(+)、CD8^(+)T细胞水平随着肿瘤巴塞罗那分期由A到D呈下降趋势,IL-6呈上升趋势.且肝硬化、HCC患者CD3^(+)(r=-0.340,P<0.001)、CD8^(+)(r=-0.353,P<0.001)T细胞水平与IL-6升高水平呈显著负相关.结论HBV相关肝硬化、HCC患者外周血CD8^(+)T细胞计数与Child分级(由A到C)呈负相关,且IL-6水平与CD8^(+)T细胞计数存在负相关关系.展开更多
基金This study was supported by a grant from Beijing Natural Science Foundation(7234399).
文摘Background:Visceral adipose tissue(VAT)has been linked to the severe acute pancreatitis(SAP)prognosis,although the underlying mechanism remains unclear.It has been reported that pyroptosis worsens SAP.The present study aimed to verify whether mesenteric adipose tissue(MAT,a component of VAT)can cause secondary intestinal injury through the pyroptotic pathway.Methods:Thirty-six male Sprague Dawley(SD)rats were divided into six different groups.Twelve rats were randomly divided into the SAP and control groups.We monitored the changes of MAT and B lymphocytes infiltration in MAT of SAP rats.Twelve SAP rats were injected with MAT B lymphocytes or phosphate buffer solution(PBS).The remaining twelve SAP rats were first injected with MAT B lymphocytes,and then with MCC950(NLRP3 inhibitor)or PBS.We collected blood and tissue samples from pancreas,gut and MAT for analysis.Results:Compared to the control rats,the SAP group showed inflammation in MAT,including higher expression of tumor necrosis factor(TNF-α)and interleukin-6(IL-6),lower expression of IL-10,and histological changes.Flow cytometry analysis revealed B lymphocytes infiltration in MAT but not T lymphocytes and macrophages.The SAP rats also exhibited intestinal injury,characterized by lower expression of zonula occludens-1(ZO-1)and occludin,higher levels of lipopolysaccharide and diamine oxidase,and pathological changes.The expression of NLRP3 and n-GSDMD,which are responsible for pyroptosis,was increased in the intestine of SAP rats.The injection of MAT B lymphocytes into SAP rats exacerbated the inflammation in MAT.The upregulation of pyroptosis reduced tight junction in the intestine,which contributed to the SAP progression,including higher inflammatory indicators and worse histological changes.The administration of MCC950 to SAP+MAT B rats downregulated pyroptosis,which subsequently improved the intestinal barrier and ameliorated inflammatory response of SAP.Conclusions:In SAP,MAT B lymphocytes aggravated local inflammation,and promoted the injury to the intestine through the enteric pyroptotic pathway.
基金supported by 16POST27490032 American Heart Association post-doctoral fellowshipNational Institute of Neurological Disorders and Stroke Exploratory Neuroscience Research Grant R21 NS114836-01A1 (to AC)
文摘As the average age of the world population increases,more people will face debilitating aging-associated conditions,including dementia and stroke.Not only does the incidence of these conditions increase with age,but the recovery afterward is often worse in older patients.Researchers and health professionals must unveil and understand the factors behind age-associated diseases to develop a therapy for older patients.Aging causes profound changes in the immune system including the activation of microglia in the brain.Activated microglia promote T lymphocyte transmigration leading to an increase in neuroinflammation,white matter damage,and cognitive impairment in both older humans and rodents.The presence of T and B lymphocytes is observed in the aged brain and correlates with worse stroke outcomes.Preclinical strategies in stroke target either microglia or the lymphocytes or the communications between them to promote functional recovery in aged subjects.In this review,we examine the role of the microglia and T and B lymphocytes in aging and how they contribute to cognitive impairment.Additionally,we provide an important update on the contribution of these cells and their interactions in preclinical aged stroke.
基金supported by grants from the National Natural Science Foundation of China(No.82020108004)the Hospital-level Clinical Innovation Military-Civilian Special Project of Army Medical University(No.2018JSLC0020)+1 种基金Chongqing Science and Technology Innovation Leading Talent(No.CSTCCXLJRC201718)Natural Science Foundation of Chongqing Innovation Group Science Program(No.cstc2021jcyj-cxttX0001).
文摘Objective:This study aimed to compare the efficacy of anti-CD19 chimeric antigen receptor T cells(CAR-T cells)versus chemotherapy plus donor lymphocyte infusion(chemo-DLI)for treating relapsed CD 19-positive B-cell acute lymphoblastic leukemia(B-ALL)after allogeneic hematopoietic stem cell transplantation(allo-HSCT).Methods:Clinical data of 43 patients with B-ALL who relapsed after allo-HSCT were retrospectively analyzed.Twenty-two patients were treated with CAR-T cells(CAR-T group),and 21 with chemotherapy plus DLI(chemo-DLI group).The complete remission(CR)and minimal residual disease(MRD)-negative CR rates,leukemia-free survival(LFS)rate,overall survival(OS)rate,and incidence of acute graft-versus-host disease(aGVHD),cytokine release syndrome(CRS)and immune effector cell-associated neurotoxicity syndrome(ICANS)were compared between the two groups.Results:The CR and MRD-negative CR rates in the CAR-T group(77.3%and 61.5%)were significantly higher than those in the chemo-DLI group(38.1%and 23.8%)(P=0.008 and P=0.003).The 1-and 2-year LFS rates in the CAR-T group were superior to those in the chemo-DLI group:54.5%and 50.0%vs.9.5%and 4.8%(P=0.0001 and P=0.00004).The 1-and 2-year OS rates in the CAR-T versus chemo-DLI group were 59.1%and 54.5%vs.19%and 9.5%(P=0.011 and P=0.003).Six patients(28.6%)with grade 2-4 aGVHD were identified in the chemo-DLI group.Two patients(9.1%)in the CAR-T group developed grade 1-2 aGVHD.Nineteen patients(86.4%)developed CRS in the CAR-T group,comprising grade 1-2 CRS in 13 patients(59.1%)and grade 3 CRS in 6 patients(27.3%).Two patients(9.1%)developed grade 1-2 ICANS.Conclusion:Donor-derived anti-CD19 CAR-T-cell therapy may be better,safer,and more effective than chemo-DLI for B-ALL patients who relapse after allo-HSCT.
文摘Bone remodeling is a tightly regulated resorption and formation of bone matrix for physiological processes or to maintain bone function. Bone remodeling involves the synchronized differentiation and activity of bone-related cell types including bone matrix-depositing osteoblasts, bone matrix-resorbing osteoclasts, collagen/extracellular matrix-producing chondrocytes, and the progenitors of these cell types. T and B cells are adaptive immune cells that can influence bone remodeling by directly regulating the function of bone-related cells under normal and pathophysiological conditions. The specific mechanisms through which T cells control remodeling are not well defined. Here, we review the impact and influence of T cells and their products on the differentiation and function of bone cells during bone remodeling. Synthesizing new connections and highlighting potential mechanisms may promote additional avenues of study to elucidate the full role that immune cells play in regulating bone homeostasis.
基金supported by the New Technology and New Project of Jinxiang Hospital Affiliated to Jining Medical University(No.JY2023026).
文摘Background:Colorectal cancer(CRC)is a common gastrointestinal malignancy.The T lymphocyte subsets are important in the develop-ment,invasion and metastasis of tumors,including CRC.Nevertheless,limited research has explored the relationship between T cell subpopu-lations and the clinical characteristics of CRC.This study compared the T lymphocyte subsets in patients with CRC and healthy individuals,and assessed the relationship between these values and clinical characteristics.Methods:Peripheral blood was collected from 100 patients with CRC and 54 healthy individuals.The numbers of CD3^(+)T,CD4^(+)T,and CD8^(+)T lymphocytes,NK cells,and the CD4^(+)T/CD8^(+)T ratio in peripheral blood were measured using flow cytometry,and were compared between CRC patients and healthy individuals.Spearman's correlation analysis was performed to investigate the relationship between the T lymphocyte subsets in patients diagnosed with CRC and the levels of carcinoembryonic antigen(CEA)and thymidine kinase 1(TK1).Receiver operating characteristic(ROC)curves were utilized to evaluate the potential utility of the T lymphocyte counts in predicting lymph node metastasis,vas-cular infiltration,and high Ki-67 expression.Results:The CRC patients had lower counts of CD3^(+)T,CD4^(+)T,and CD8^(+)T lymphocytes compared to the healthy population(P<0.05).However,no significant differences were observed in the CD4^(+)/CD8^(+)ratio or NK cells(P>0.05).Notably,the CD3^(+)T,CD4^(+)T,and CD8^(+)T lym-phocyte counts were higher in patients with stageⅠ-Ⅱdisease,no lymph node metastasis,no vascular invasion,and low Ki-67 expression than in those with stageⅢ,lymph node metastasis,vascular invasion,and high Ki-67 expression(P<0.05).There was a negative association be-tween the CD3^(+)T,CD4^(+)T,and CD8^(+)T lymphocyte counts and CEA and TK1 levels in patients with CRC.The ROC curves demonstrated that CD3^(+)T,CD4^(+)T,and CD8^(+)T lymphocyte counts had significant predictive value for lymph node metastasis,vascular infiltration,and high Ki-67 expression.Conclusions:The peripheral blood CD3^(+)T,CD4^(+)T,and CD8^(+)T lymphocyte counts are related to the clinical traits of patients with CRC and can predict the prognosis of the disease.
文摘旨在通过免疫信息学方法预测非洲猪瘟病毒(ASFV)结构蛋白的T、B细胞表位,为非洲猪瘟(ASF)表位疫苗的设计研制提供参考。从NCBI和RCSB数据库获取ASFV蛋白质序列和三维结构,利用IEDB、DTU Health Tech等数据库的生物信息学工具对ASFV的5种结构蛋白p72、p17、p49、M1249L和H240R的细胞毒性T细胞表位、线性B细胞和构象B细胞表位进行鉴定。结果显示:5种蛋白质均为亲水性,二级结构以无规则卷曲为主,仅M1249L例外;预测到抗原性良好、无毒、无致敏的细胞毒性T细胞优势表位27个,线性B细胞优势表位35个;预测到仅针对p72的构象B细胞优势表位2个。结论:ASFV的5种蛋白质可能具有多个潜在T、B细胞表位,其中B细胞表位相对占优,5种蛋白质中p72和M1249L最具疫苗研发前景,可结合蛋白质相关参数信息为构建ASF表位疫苗提供参考。