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Why should lymphocytes immune profile matter in sepsis?

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World Journal of Critical Care Medicine 2025年第2期14卷 18-26页

作者： Wagner Nedel Lílian R Henrique Luis Valmor Portela Department of Intensive Care Unit Conceição Hospital GroupPorto Alegre 91350200Brazil Department of Biochemistry Institute of Basic Health SciencesFederal University of Rio Grande do SulPorto Alegre 90035-003Brazil

The global incidence of critical illness has been steadily increasing,resulting in higher mortality rates thereby presenting substantial challenges for clinical *** these conditions,sepsis stands out as the leading cause of critical illness,underscoring the urgent need for continued research to enhance patient care and deepen our understanding of its complex ***-cytes play a pivotal role in both innate and adaptive immune responses,acting as key regulators of the balance between pro-inflammatory and anti-inflam-matory processes to preserve immune *** the context of sepsis,an impaired immunity has been associated with disrupted lymphocytic metabolic activity,persistent pro-inflammatory state,and subsequent *** disruptions not only impair pathogen clearance but also predispose pati-ents to secondary infections and hinder recovery,highlighting the importance of targeting lymphocyte dysfunction in sepsis ***,studies have identified absolute lymphocyte counts and derived parameters as promising clinical biomarkers for prognostic assessment and therapeutic *** particular,neutrophil-to-lymphocyte ratio,and lymphopenia have gained reco-gnition in the literature as a critical prognostic markers and therapeutic target in the management of *** review aims to elucidate the multifaceted role of lymphocytes in pathophysiology,with a focus on recent advancements in their use as biomarkers and key findings in this evolving field.

关键词： lymphocytes Neutrophil-to-lymphocyte ratio Sepsis Septic shock Chronic critical illness Persistent inflammation,immunosuppression,and catabolism syndrome

Oxidative stress and apoptosis of Carassius auratus lymphocytes induced by nonplanar (PCB153) and coplanar (PCB169) polychlorinated biphenyl congeners in vitro

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Journal of Environmental Sciences 2009年第9期21卷 1284-1289页

作者： ZHANG Jianying ZHANG Hangjun NI Wanmin College of Environmental and Resource Sciences Zhejiang University Hangzhou 310028 China. College of Life and Environmental Sciences Hangzhou Normal University Hangzhou 310036 China

Among all the 209 kinds ofpolychlorinated biphenyls （PCBs） congeners, nonplanar and coplanar PCB congeners have different levels of toxicity on mammal cells such as neuronal cells, but little is known about their toxicity on fish cells although PCB congeners usually have high bioaccumulation abilities in the detected fish bodies. This study showed that 2,2＇,4,4＇,5,5＇-hexacholorbiphenyl （PCB 153, nonplanar congener） and 3,3＇,4,4＇,5,5＇-hexacholorbiphenyl （PCB 169, coplanar congener） caused apoptosis on the isolated crucian carp （Carassius auratus） lymphocytes and the induced cytotoxicity was structure-dependent. According to the laser confocal microscope observations, apoptosis was clearly distinguished by condensation of nucleus, shrinkage and formation of apoptotic bodies. DNA fragmentation was detected by agarose gel electrophoresis. These typical morphological and biochemical characteristics indicate the occurrence of apoptosis on fish lymphocytes. According to the flow cytometry analysis, after the cells were exposed to 10 μmol/L PCBs for 3 h, the apoptotic percentage induced by PCB153 was 23.41%, while that induced by PCBI69 was even higher （31.03%）. Furthermore, incubating PCBs with fish lymphocytes enhanced levels of reactive oxygen species （ROS） and malondialdehyde （MDA）, clearly indicating the presence of oxidative stress and lipid peroxidation. Our data also demonstrate that the different cytotoxic effects induced by coplanar and nonplanar PCBs were correlated with their structural characteristics and the coplanar congener was more cytotoxic than nonplanar congener. This study suggests that cytotoxicity mechanisms of the PCB congeners on fish lymphocytes depend on their planarity and chemical structures.

关键词： apoptosis lymphocytes malondialdehyde (MDA) reactive oxygen species (ROS)

Estrogen-mediated downregulation of HIF-1αsignaling in B lymphocytes influences postmenopausal bone loss

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Bone Research 2022年第2期10卷 326-337页

作者： Xianyi Meng Zhen Lin Shan Cao Iga Janowska Koshiro Sonomoto Darja Andreev Knab Katharina Jinming Wen Karl Xaver Knaup Michael Sean Wiesener Gerhard Krönke Marta Rizzi Georg Schett Aline Bozec Department of Internal Medicine 3 Friedrich-Alexander-University Erlangen-Nürnberg(FAU)and Universitätsklinikum ErlangenErlangen 91054Germany Deutsches Zentrum fur Immuntherapie(DYI) Erlangen 91054Germany Department of Rheumatology and Clinical Immunology Faculty of MedicineMedical Center-University of FreiburgFreiburg 79106Germany Department of Internal Medicine 4 Friedrich-Alexander-University Erlangen-Nürnberg(FAU)and Universitätsklinikum ErlangenErlangen 91054Germany

In the bone marrow, B cells and bone-resorbing osteoclasts colocalize and form a specific microenvironment. How B cells functionally influence osteoclasts and bone architecture is poorly understood. Using genetically modified mice and highthroughput analyses, we demonstrate that prolonged HIF-1α signaling in B cells leads to enhanced RANKL production and osteoclast formation. In addition, deletion of HIF-1α in B cells prevents estrogen deficiency-induced bone loss in ***, estrogen controls HIF-1α protein stabilization through HSP70-mediated degradation in bone marrow B *** stabilization of HIF-1α protein in HSP70-deficient bone marrow B cells promotes RANKL production and *** of HSP70 expression by geranylgeranylacetone(GGA) administration alleviates ovariectomy-induced ***, RANKL gene expression has a positive correlation with HIF1 A expression in human B cells. In conclusion, HIF-1αsignaling in B cells is crucial for the control of osteoclastogenesis, and the HSP70/HIF-1α axis may serve as a new therapeutic target for osteoporosis.

关键词： mediated lymphocytes stabilization

Innate lymphocytes-lineage,localizationandtimingof differentiation

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Cellular & Molecular Immunology 2019年第7期16卷 627-633页

作者： Emily R.Kansler Ming O.Li Immunology Program Sloan Kettering InstituteMemorial Sloan Kettering Cancer CenterNew YorkNY10065USA Louis V.Gerstner Jr.Graduate School of Biomedical Sciences Memorial Sloan Kettering Cancer CenterNew YorkNY10065USA

Innate lymphocytes are a diverse population of cells that carry out specialized functions in steady-state homeostasis and during immune *** circulating cytotoxic natural killer(NK)cells have been studied for decades,tissue-resident innate lymphoid cells(ILCs)have only been characterized and studied over the past few *** ILCs have been largely viewed in the context of helper T-cell biology,models of ILC lineage and function have been founded within this ***,tissue-resident innate lymphocytes with cytotoxic potential have been described in an array of tissues,yet whether they are derived from the NK or ILC lineage is only beginning to be *** this review,we aim to shed light on the identities of innate lymphocytes through the lenses of cell lineage,localization,and timing of differentiation.

关键词： lymphocytes lineage homeostasis

Effects of Sterigmatocystin, Deoxynivalenol and Aflatoxin G_1 on Apoptosis of Human Peripheral Blood lymphocytes in vitro

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Biomedical and Environmental Sciences 2002年第2期15卷 145-152页

作者： SunXM等 ZhangXH 等 DepartmentofExperimentalPathology HebeiMedicalUniversityShijiazhuang050017HebeiChina

Objective To explore the effects of Sterigmatocystin (ST), Deoxynivalenol (DON) and Aflatoxin G1 (AFG1) on apoptosis of human peripheral blood lymphocytes (HPBLs) in vitro and thus to further elucidate the putative roles of these three mycotoxins on human immunosystem. Methods The effects of ST, DON and AFG1 on apoptosis of HPBLs were studied with cell culture, flow cytometric (FCM) DNA analysis and DNA agarose gel electrophoresis. Results DNA agarose gel electrophoresis results showed the characteristic 'ladder' pattern of apoptosis in HPBLs treated with ST, DON and AFG1. Flow cytometric DNA analysis revealed that typical subdiploid peaks of apoptosis in DNA histogram could be seen in all groups treated with the three mycotoxins. Significant time-effect and dose-effect relationships were found between the apoptosis rates and treatment time as well as concentrations of the three mycotoxins. Conclusion ST, DON and AFG1 can induce apoptosis of HPBLs in vitro and may have some negative effects on human immunosystem.

关键词： Sterigmatocystin Deoxynivalenol Aflatoxin G1 Apoptosis Human lymphocytes

Prognostic value of tertiary lymphoid structure and tumour infiltrating lymphocytes in oral squamous cell carcinoma

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International Journal of Oral Science 2020年第3期12卷 227-234页

作者： Qunxing Li Xiangqi Liu Dikan Wang Yanqiong Wang Huanzi Lu Shuqiong Wen Juan Fang Bin Cheng Zhi Wang Hospital of Stomatology Guanghua School of StomatologyGuangdong Provincial Key Laboratory of StomatologySun Yat-Sen UniversityGuangzhouChina

Tertiary lymphoid structures(TLS)are ectopic lymphoid structures in cancers that are largely associated with favourable ***,the prognostic value of TLSs in oral squamous cell carcinoma(OSCC)is largely unknown,and the association between tumour infiltrating lymphocytes(TILs)and TLSs has been rarely explored in *** this study,associated markers of TLS,including peripheral node address(PNAd)in high endothelial venules,CD20 in B cells and CD3 in T cells,were examined in 168 OSCC patients,and survival analysis was performed between TLS-positive and TLS-negative *** detected the presence of TILs by staining CD8+cytotoxic T cells and CD57+NK cells as *** appeared as highly organized structures in 45(26.8%)*** patients had a better 5-year overall survival(OS)rate(88.9%vs.56.1%,P<0.001)and relapse-free survival(RFS)rate(88.9%vs.63.4%,P=0.002).Moreover,the presence of TLS was an independent prognostic factor for both the 5-year OS rate(hazard ratio[HR]=3.784;95%confidence interval[CI],1.498–9.562)and RFS rate(HR=3.296;95%CI,1.279–8.490)in multivariate ***,a higher density of CD8+T cells and CD57+NK cells was found in TLS-positive sections than in TLS-negative counterparts(P<0.001),and their combination provided a higher predictive accuracy(AUC=0.730;95%CI,0.654–0.805).In conclusion,our results suggest that TLS is an independent positive prognostic factor for OSCC *** findings provide a theoretical basis for the future diagnostic and therapeutic value of TLSs in OSCC treatment.

关键词： lymphocytes lymphoid infiltrating

ACE2-independent infection of T lymphocytes by SARS-CoV-2

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Signal Transduction and Targeted Therapy 2022年第4期7卷 1232-1242页

作者： Xu-Rui Shen Rong Geng Qian Li Ying Chen Shu-Fen Li Qi Wang Juan Min Yong Yang Bei Li Ren-Di Jiang Xi Wang Xiao-Shuang Zheng Yan Zhu Jing-Kun Jia Xing-Lou Yang Mei-Qin Liu Qian-Chun Gong Yu-Lan Zhang Zhen-Qiong Guan Hui-Ling Li Zhen-Hua Zheng Zheng-Li Shi Hui-Lan Zhang Ke Peng Peng Zhou CAS Key Laboratory of Special Pathogens&State Key Laboratory of Virology Wuhan Institute of VirologyChinese Academy of SciencesWuhanPeople’s Republic of China University of Chinese Academy of Sciences BeijingPeople’s Republic of China State Key Laboratory of Genetic Engineering School of Life SciencesZhongshan HospitalFudan University200438 ShanghaiChina Center for Organoid and Regenerative Medicine Greater Bay Area Institute of Precision Medicine(Guangzhou)511462 GuangzhouChina Department of Respiratory and Critical Care Medicine Tongji HospitalTongji Medical CollegeHuazhong University of Science and TechnologyJie Fang RoadHan Kou District430030 WuhanChina

SARS-CoV-2 induced marked lymphopenia in severe patients with ***,whether lymphocytes are targets of viral infection is yet to be determined,although SARS-CoV-2 RNA or antigen has been identified in T cells from ***,we confirmed that SARS-CoV-2 viral antigen could be detected in patient peripheral blood cells(PBCs)or postmortem lung T cells,and the infectious virus could also be detected from viral antigen-positive *** next prove that SARS-CoV-2 infects T lymphocytes,preferably activated CD4+T cells in *** infection,viral RNA,subgenomic RNA,viral protein or viral particle can be detected in the T ***,we show that the infection is spike-ACE2/TMPRSS2-independent through using ACE2 knockdown or receptor blocking ***,we demonstrate that viral antigen-positive T cells from patient undergone pronounced *** vitro infection of T cells induced cell death that is likely in mitochondria ROS-HIF-1a-dependent ***,we demonstrated that LFA-1,the protein exclusively expresses in multiple leukocytes,is more likely the entry molecule that mediated SARS-CoV-2 infection in T cells,compared to a list of other known ***,this work confirmed a SARS-CoV-2 infection of T cells,in a spike-ACE2-independent manner,which shed novel insights into the underlying mechanisms of SARS-CoV2-induced lymphopenia in COVID-19 patients.

关键词： ACE2 lymphocytes infection

Intraepithelial lymphocytes: bystanders or causative factors in functional gastrointestinal disorders?

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Cellular & Molecular Immunology 2021年第7期18卷 1620-1621页

作者： Giuseppe Losurdo Domenico Piscitelli Enzo Ierardi Alfredo Di Leo Section of Gastroenterology Department of Emergency and Organ TransplantationUniversity of BariBariItaly Ph.D.Course in Organs and Tissues Transplantation and Cellular Therapies Department of Emergency and Organ TransplantationUniversity of BariBariItaly Section of Pathology Department of Emergency and Organ TransplantationUniversity of BariBariItaly

Intraepithelial lymphocytes(IELs)are immune cells located in the epithelium of the mucosal layer of the gastrointestinal tract that typically show a CD3-positive *** are T lymphocytes that are involved in the primary immune response to several luminal antigens,such as food proteins and infectious *** this reason,their increase may be pathogenetic in several diseases,the most important being celiac ***,an increase above 25 IELs/100 enterocytes in the duodenum,which is considered the cutoff value for celiac disease,may occur in several conditions,such as nonceliac gluten sensitivity,food allergy,Helicobacter pylori(***)infection,gastroenteritis,and even irritable bowel syndrome(IBS).Therefore,the generic term“microscopic enteritis”or“duodenal lymphocytosis”has been proposed for this condition.

关键词： lymphocytes gastrointestinal epithelium

Study on the effects of cefotaxime on intracellular Ca^(2+) in human peripheral lymphocytes by fluoremetry

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Chinese Chemical Letters 2007年第4期18卷 424-426页

作者： Dan Dan Wang Hai Yan Wang Ye Hong Zhou Chun Gui Zhao Chuan Dong Shao Min Shuang School of Chemistry and Chemical Engineering Shanxi University Taiyuan 030006 China Medical College of Shanxi Datong University Datong 037000 China

Characteristic of Fura-2-Ca^2＋ interaction was studied based on the fluorescence technique. The apparent dissociation constants （Kd） of the Fura-2-Ca^2＋ complex were determined at different temperature. The effect of cefotaxime （CEFA） on intracellular Ca^2＋ concentration （[Ca^2＋]i） was discussed by using a ratiometric fluorescence dye Fura-2 as a probe. The basal [Ca^2＋]i in resting human peripheral lymphocytes was 100 4- 7 nmol/L but after treatment with cefotaxime, the changes of [Ca^2＋]i were observed in different conditions. In the concentration range of 1-30 μmol/L of cefotaxime [Ca^2＋]i increased, as a result of releasing intracellular Ca^2＋ stores. Higher concentration of cefotaxime （50-500 μmol/L） stimulated to decrease of [Ca^2＋]i.

关键词： Fura-2 lymphocytes Cefotaxime [Ca^2+]i