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Genomics, Proteomics & Bioinformatics 2007年第3期5卷 216-235页

作者： Frankie B.Stentz Abbas E.Kitabchi Division of Endocrinology Diabetes and MetabolismDepartment of MedicineThe University of Tennessee Health Science CenterMemphisTN 38163USA.

We analyzed the genes expressed （transcriptomes） and the proteins translated （pro- teomes） in muscle tissues and activated CD4^＋ and CD8^＋ t-lymphocytes （t-cells） of five type 2 diabetes （t2DM） subjects using Affymetrix microarrays and mass spectrometry, and compared them with matched non-diabetic controls. Gene expressions of insulin receptor （INSR）, vitamin D receptor, insulin degrading enzyme, Akt, insulin receptor substrate-1 （IRS-1）, IRS-2, glucose transporter 4 （GLUt4）, and enzymes of the glycolytic pathway were decreased at least 50% in t2DM than in controls. However, there was greater than two-fold gene upregulation of plasma cell glycoprotein-1, tumor necrosis factor a （tNFα）, and gluconeogenic enzymes in t2DM than in controls. the gene silencing for INSR or tNFα resulted in the inhibition or stimulation of GLUt4, respectively. Proteome profiles corresponding to molecular weights of the above translated transcriptomes showed different patterns of changes between t2DM and controls. Meanwhile, changes in transcriptomes and proteomes between muscle and activated t-cells of t2DM were comparable. Activated t-cells, analogous to muscle cells, expressed insulin signaling and glucose metabolism genes and gene products. In conclusion, t-cells and muscle in t2DM exhibited differences in expression of certain genes and gene products relative to non-diabetic controls. these alterations in transcriptomes and proteomes in t2DM may be involved in insulin resistance.

关键词： genomics proteomics t-lymphocytes activation muscle type 2 diabetes

Enhanced interferon-y secretion and antitumor activity of t-lymphocytes activated by dendritic cells loaded with glycoengineered myeloma antigens

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Chinese Medical Journal 2007年第19期120卷 1678-1684页

作者： XIONG Hong WU Qiu-ye HU Hong-gang LIU Ban GUO Zhong-wu Daniel Man-yuan Sze HOU Jian Department of Hematology Shanghai Changzheng Hospital Second Military Medical University Shanghai 200003 China School of Pharmacy Second Military Medical University Shanghai 200433 China Department of Chemistry Wayne State University 5101 Cass Avenue Detroit Michigan 48202 USA Institute of Hematology Royal Prince Alfred Hospital University of Sydney Missenden Road Camperdown Sydney NSW2050 Australia

Background Immunotherapy is emerging as a promising cure for cancer. However, a severe problem in this area is the immune tolerance to tumor cells and tumor-associated antigens, as evidenced by the ability of cancer to escape immune surveillance. to overcome this problem this work examined the potential of improving the antigenicity of myeloma by metabolic engineering of its cell surface carbohydrate antigens （i.e., glycoengineering） and presentation of the modified tumor antigens by dendritic cells （DCs） to generate cytotoxic t-lymphocytes （CtLs）. Methods CD138^＋ myeloma cells were isolated from 11 multipe myeloma （MM） patients by the immunomagnetic bead method. the MM cells were treated with N-propionyI-D-mannosamine （ManNPr）, a synthetic analog of N-acetyl-D-mannosamine （ManNAc）, the natural biosynthetic precursor of N-acetyl sialic acid （NeuNAc）, to express unnatural N-propionylated sialoglycans. the glycoengineered cells were then induced to apoptosis, and the apoptotic products were added to cultured functional DCs that could present the unnatural carbohydrate antigens to autologous t-lymphocytes. Results It was found that the resultant DCs could activate CD4^＋ and CD8^＋ t-lymphocytes, resulting in increased expression of t cell surface markers, including CD8CD28 and CD4CD29. Moreover, upon stimulation by glycoengineered MM cells, these DC-activated t-lymphocytes could release significantly higher levels of IFN-y （P〈0.05）. Lactate dehydrogenase （LDH） assays further showed that the stimulated t-lymphocytes were cytotoxic to glycoengineered MM cells. Conclusions this work demonstrated that glycoengineered myeloma cells were highly antigenic and the CtLs induced by the DCs loaded with the unnatural myeloma antigens were specifically cytotoxic to the glycoengineered myeloma. this may provide a new strategy for overcoming the problem of immune tolerance for the development of effective immunotherapies for MM.

关键词： multiple myeloma dendritic cells t-lymphocytes immunotherapy

Electroacupuncture Attenuates Surgical Stress-Induced Reduction of t lymphocytes through Modulation of Peripheral Opioid System

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Chinese Journal of Integrative Medicine 2021年第2期27卷 98-105页

作者： WANG Ke YONG Yue ZHOU Jia ZHOU Wen-xiong GUO Jun CHEN tong-yu Department of Cardiothoracic Surgery Yueyang Hospital of Integrated Traditional Chinese and Western MedicineShanghai University of Traditional Chinese MedicineShanghai(200437)China Institute of Clinical Immunology Yueyang Hospital of Integrated Traditional Chinese and Western MedicineShanghai University of Traditional Chinese MedicineShanghai(200437)China Research Institute of Acupuncture Anesthesia Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese MedicineShanghai(201203)China Department of Anesthesiology Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese MedicineShanghai(201203)China

Objective:to investigate the action mechanisms of electroacupuncture(EA)on postoperative ***:Male C57 BL/6 mice(5–7 weeks old)were randomly divided into:the sham injury group,the surgical trauma stressed group,the EA group[surgery+2/100 Hz EA at Neiguan(PC 6)],and the EA+Nal(surgery+EA+intraperitoneal injection of naloxone).Abdominal surgical trauma stress mice model was *** was performed on bilateral PC 6 acupoints by an EA apparatus(2/100 Hz)for 20 min once a day for 3 *** m RNA expressions of MOR,DOR,and KOR in thymus and L3-5 dorsal root ganglions(DRG)were determined by quantitative real-time polymerase chain reaction(q Rt-PCR)and the protein expressions of MOR,DOR,and KOR in thymus were measured by Western *** cytometry assay was used to detect the levels of t lymphocyte subtypes in the peripheral ***:Surgical trauma induced decreased the m RNA expression level of MOR in both thymus(Ptreatment not only significantly attenuated the MOR protein and m RNA expression in the thymus(both Pt also markedly increased expression of DOR and KOR opioid receptor in thymus(Pthe m RNA expressions of opioid receptors were not regulated by EA in the DRG(all P>0.05).Furthermore,t lymphocyte population of CD3^+ and CD4^+ was decreased in the peripheral blood after surgical trauma(both Ptreatment can significantly elevate the population of CD3^+(Pt cells(Ptraperitoneal injection of the non-selective opioid receptor antagonist naloxone blocked the up-regulation of t lymphocytes by ***:EA may improve postoperative immunosuppression through the peripheral opioid system.

关键词： electroacupuncture Chinese medicine immunosuppression opioid receptor t-lymphocytes

Proteomics Analysis of t lymphocytes Damage Induced by Ionizing Irradiation

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Chinese Journal of Chemistry 2011年第1期29卷 159-164页

作者： Shi, Ying Zhang, Xuan Liu, Ning Liang, Feng Song, Fengrui Liu, Zhiqiang Liu, Shuying Changchun Institute of Applied Chemistry Chinese Academy of Sciences Changchun Jilin 130022 China School of Public Health Jilin University Changchun Jilin 130021 China Central Laboratory The Second Hospital of Jilin University Changchun Jilin 130041 China College of Pharmacy Jilin University Changchun Jilin 130021 China Graduate School of the Chinese Academy of Sciences Beijing 100039 China

Human t lymphocytes were found to be highly radiosensitive and complex cellular responses including apoptosis could be induced upon exposure to X-ray irradiation. However, the mechanism of apoptosis associated with irradiation was not clear. In this study, a proteomic method was applied to investigation on alteration of proteome of human t-lymphocyte cells after irradiation. the Jurkat cells were irradiated with 4 Gy X-ray and the cell lysates were collected at different times after irradiation （6, 12, 18, 24 and 48 h）. the whole proteins were separated and quantified by two-dimensional fluorescence difference gel electrophoresis, and then the differentially expressed proteins were identified by mass spectrometry. 4 proteins exhibited significant irradiation-induced difference in abundance, including L-plastin, bifunctional purine biosynthesis protein, tubulin beta chain, beta-actin. Differentially expressed proteins were reported to be directly or indirectly involved in the function of human t lymphocyte. thus, this study might provide clues to identify proteins with biological significance related to irradiation.

关键词： t-lymphocytes irradiation electrophoresis apoptosis proteomics L-plastin

Activation and coreceptor expression of t lymphocytes induced by highly active antiretroviral therapy in Chinese HIV/AIDS patients

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Chinese Medical Journal 2006年第23期119卷 1966-1971页

作者： ZHANG Zi-ning SHANG Hong JIANG Yong-jun LIU Jing DAI Di DIAO Ying-ying GENG Wen-qing JIN Xin WANG Ya-nan Key Laboratory of Immunology of AIDS Ministry of Health FirstAffiliated Hospital China Medical University Shenyang 110001China

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 activation markers, CCR5 and the CD4^＋ t lym

关键词： human immunodeficiency virus type-l antiretroviral therapy, highly active t-lymphocytes activation analysis

Down-regulation of human leukocyte antigens class I on peripheral t lymphocytes and NK cells from subjects in region of high-incidence gastrointestinal tumor

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Chinese Medical Journal 2011年第12期000卷 1813-1817页

作者： ZHANG Zhi-mian LI Ying-jie GUAN Xiao YANG Xiao-yun GAO Xi-mei YANG Xiao-jing WANG Li-shui ZOU Xiong Department of Health Examination Center Qilu Hospital of Shandong University Jinan Shandong 250012 China Department of Laboratory Medicine Qilu Hospital of Shandong University Jinan Shandong 250012 China

Background Many types of human tumors can suppress the immune system to enhance their survival. Loss or down-regulation of human leukocyte antigens （HLA） class I on tumors is considered to be a major mechanism of tumor immune escape. Our previous studies found that HLA class I on peripheral-blood mononuclear cells was significantly lower in gastric cancer patients. the present study made an analysis of HLA class I expression on peripheral-blood t lymphocytes and NK cells from subjects of Lijiadian village, a village with high-incidence gastrointestinal tumor. Methods A total of 181 villagers from Lijiadian village and 153 normal controls from the Department of Health Examination Center were enrolled in this study. Using a multi-tumor markers detection system, these villagers were divided into two groups： high-risk group （tumor markers positive group） and low-risk group （tumor markers negative group）. the percentage of t lymphocytes and NK cells and levels of HLA class I on their surface were determined in these subjects by flow cytometry. Results Percentages of t lymphocytes and NK cells in peripheral-blood mononuclear cells did not vary with age. the expression level of HLA class I on peripheral t lymphocytes and NK cells was not affected by age or gender, but was significantly down-regulated in Lijiadian villagers （P 〈0.05）, with the low-risk group, there was a significant reduction of cells （P 〈0.05） in the high-risk group. especially on the surface of NK cells （P 〈0.01）. Compared HLA class I on peripheral t lymphocytes （P 〈0.05） and NK Conclusions HLA class I on peripheral t lymphocytes and NK cells may be involved in tumorigenesis and development of gastrointestinal tumor, and understanding their changes in expression may provide new insights into the mechanism of tumor immunity.

关键词： histocompatibility antigens class I t-lymphocytes killer cells, natural gastrointestinal neoplasms

Induction of systemic lupus erythematosus syndrome in BALB/c mice by immunization with active chromatin

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Acta Pharmacologica Sinica 2004年第6期25卷 105-109页

作者： Hong LI, Yun-yi ZHANG, Ya-nan SUN, Xi-yi HUANG, Yong-feng JIA, Duan LI2 Department of Pharmacology, Schoolof Pharmacy, Fudan University, Shanghai 200032, China Department of Pharmacology School of Pharmacy Fudan University Shanghai 200032 China

AIM: to establish an animal model for systemic lupus erythematosus (SLE)-like syndrome in mice. MEtHODS: BALB/c mice were immunized with active chromatin isolated from ConA-actived syngeneic spleno-lymphocytes. Plasma samples of mice were tested by enzyme-linked immunosorbent assays (ELISA) for the presence of IgG anti-dsDNA, -ssDNA, and anti-histone antibodies. tumor necrosis factor-α (tNF-α) in serum was measured by ELISA. Spleno-lymphocyte proliferation assays and the levels of interferon-γ (IFN-γ) in supernatants were tested respectively. Proteinuria was measured. Kidneys were examined by direct immunohistochemical method and light microscopy. RESULtS: Anti-ds DNA, ssDNA, and histone antibodies were induced in active chromatin-immu- nized mice, the proliferation response of splenocytes to ConA and LPS were reduced, levels of interferon-γ in supernatants and tNF-α in serum were lowered. Lupus nephritis was assessed by the presence of Ig deposits, glomerular pathology and proteinuria. CONCLUSION: the active chromatin-induced SLE-like mouse model was similar to idiopathic SLE in human.

关键词： systemic lupus erythematosus chromatin autoantibody tumor necrosis factor interferon type II B-lymphocytes t-lymphocytes female enzyme-linked immunosorbent assay

Immunomodulatory effects and mechanisms of plant alkaloid tetrandrine in autoimmune diseases

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Acta Pharmacologica Sinica 2002年第12期23卷 40-48页

作者： LAI Jenn-HaungRheumatology/Immunology and Allergy, Department of Medicine, tri-Service General Hospital, National Defense Medical Center, taipei, taiwan, China Rheumatology/Immunology and Allergy Department of Medicine Tri-Service General Hospital National Defense Medical Center Taipei Taiwan China

Autoimmune diseases characterized by activation of immune effector cells and damage of target organs are currently treated with a combination of several disease-modifying antirheumatic drugs (DMARDs) that preserve different immunomodulatory mechanisms. Such a combination treatment strategy not only provides synergistic effects but also reduces side effects from individual drug. tetrandrine (tet), purified from a creeper Stephania tetrandra S Moore, is a bis-benzylisoquinoline alkaloid and has been used to treat patients with silicosis, autoim-mune disorders, and hypertension in China’s mainland for decades. the accumulated studies both in vitro and in vivo reveal that tet preserves a wide variety of immunosuppressive effects. Importantly, the tet-mediated immu-nosuppressive mechanisms are evidently different from some known DMARDs. the synergistic effects have also been demonstrated between tet and other DMARDs like FK506 and cyclosporin. these results highlight tet a very potential candidate to be consid

关键词： tetrandrine t-lymphocytes autoimmune diseases alkaloids

Protective effects of Jiayan Kangtai granules on autoimmune thyroiditis in a rat model by modulating th17/treg cell balance

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Journal of traditional Chinese Medicine 2018年第3期38卷 380-390页

作者： Hou Yi Wang tieshan Guo Xiangyu Sun Wen Guo Xuan Wu Lili Qin Lingling Zhang Chengfei Liu tonghua Key Laboratory of Health Cultivation of the Ministry of Education Beijing University of Chinese Medicine Beijing 100029 China Dongfang Hospital of Beijing University of Chinese Medicine Beijing 100078 China Beijing Research Institute of Chinese Medicine & Beijing University of Chinese Medicine Beijing100029 China Department of Endocrinology Dongfang Hospital of Beijing University of Chinese Medicine Beijing100078 China Beijing Key Laboratory of Health Cultivation Beijing University of Chinese Medicine Beijing 100029China Science and technology Department Beijing University of Chinese Medicine Beijing 100029 China

OBJECtIVE: to investigate the protective effects of Jiayan Kangtai(JYKt) granules, consisting of 9 Chinese herbs, in a rat model of autoimmune thyroiditis(AIt), and the possible underlying ***: Female Lewis rats(6-8 weeks) were randomly apportioned to 5 groups of 10, including a normal control. AIt was induced in the untreated AIt-model group, and rats treated subsequently with daily low, medium, or high dose JYKt granules. After 12 weeks, plasma levels of thyroid autoantibodies and morphological changes in the thyroid were detected by enzyme-linked immunosorbent assay and histological examination, respectively. the presence of interleukin(IL)-6,IL23 p19, and IL-2 in thyroid tissue was assessed by immunohistochemical staining. the percentages of t helper(th)17 cells and regulatory t cells(tregs) in the peripheral blood were analyzed by flow cytometry. Relevant levels of cytokines and proteins were examined via bead-based multiplex flow cytometry and ELISA, respectively. Expressions of genes and proteins regulated by th17 cells and tregs were shown by real-time PCR and Western ***: Compared to the control, AIt-model rats had higher plasma concentrations of thyroid autoantibodies. the high-dose JYKt rats showed significantly lower levels of thyroid autoantibodies compared with the AIt model group. Rats in the AIt-JYKt groups also had fewer thyroid lesions and less lymphocytic infiltration, a lower percentage of th17 cells, and a higher percentage of tregs, compared with the AIt-model. Rats given high-dose JYKt had a significantly lower th17/treg ratio compared with the AIt model. Differences in plasma cytokine concentrations and relevant gene and protein expressions in the spleens of JYKt-treated rats and the AIt group suggested an association between JYKt treatment and lower th17 cell percentage and higher treg ***: JYKt treatment appeared to be protective against AIt in rats, possibly via the regulation of the th17 cell/treg im

关键词： thyroiditis autoimmune th17 cells t-lymphocytes regulatory Herbal medicine Jiay-an Kangtai granules

Sterile alpha motif and histidine-aspartic acid domain-containing protein 1 expression and its relationship with t cell activation in human immunodeficiency virus/acquired immune deficiency syndrome patients with lung-spleen Qi deficiency syndrome pattern

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Journal of traditional Chinese Medicine 2022年第3期42卷 451-457页

作者： LIU Zhen ZHANG Qingyan DENG Bowen SANG Feng WANG Danni KANG Ning LI Jie ZHANG Min LIANG Shoupei DUAN Chenchen LIU Zhibin XU Qianlei LI Qiang Henan Key Laboratory of Viral Diseases Prevention and treatment of traditional Chinese Medicine the First Affiliated Hospital of Henan University of Traditional Chinese MedicineZhengzhou 450000China Department of Acquired Immune Deficiency Syndrome treatment and Research Center The First Affiliated Hospital of Henan University of Traditional Chinese MedicineZhengzhou 450000China Department of Obstetrics and Gynecology the First Affiliated Hospital of Henan University of Traditional Chinese MedicineZhengzhou 450000China Medical Department Medical Department of Zhengzhou People’s HospitalZhengzhou 450000China

OBJECtIVE:to investigate the relationship between antiviral restriction factor Sterile Alpha Motif and Histidine-Aspartic acid domain-containing protein 1(SAMHD1)expression and t cell activation,furthermore,identifying objective indexes of lung-spleen Qi deficiency symptom ***:We assessed the profile of t lymphocyte subsets,characteristics of SAMHD1 and human leukocyte antigen DR(HLA-DR)expression in lungspleen Qi deficiency *** the same time,people living with human immunodeficiency virus/acquired immune deficiency syndrome(HIV/AIDS)(PLWHA)without obvious clinical symptoms and healthy donors in this area were used as ***:Immunohematologic indexes lower CD4 count,lower CD4/CD8 ratio and higher SAMHD1 level were found in lung-spleen Qi deficiency ***,we demonstrated a positive relationship between SAMHD1 and HLA-DR level as well as with interferon factor in lung-spleen Qi deficiency syndrome and patients without obvious clinical signs and symptoms ***:these data indicated the positive relationship between SAMHD1 and t cell activation which further elucidated the role of SAMHD1 in cellular immune ***,combination of t lymphocyte subsets counts and SAMHD1 level may be used as clinical and biological reference basis for the differentiation and diagnosis of HIV/AIDS traditional Chinese medicine syndromes.

关键词： HIV acquired immunodeficiency syndrome symptoms complex SAM domain and HD domain-containing protein 1 t-lymphocytes