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Effect of Dihydrotestosterone on costimulatory molecules in a Mouse Model of Graves’ Disease

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Chinese Medical Sciences Journal 2020年第3期35卷 215-225页

作者： Lianye Liu Bingyin Shi Fengyi Zhao Peng Hou Shu Liu Xiaomei Liu Liping Wu Department of Endocrinology The First Affiliated Hospital of Xi’an Jiaotong UniversityXi’an 710061China Department of Endocrinology Weinan Central HospitalWeinanShaanxi 714000China Department of Endocrinology Nanjing First HospitalNanjing Medical UniversityNanjing 210001China

Objective Graves’disease is the most common autoimmune thyroid disease and its prevalence and clinical manifestations are disparate between females and *** molecules play an essential role in regulating autoimmune *** objective of this study was to determine if expression of inhibitory molecules was correlated with treatment by dihydrotestosterone(DHT)in an in vivo BALB/c mouse model of experimental autoimmune Graves’*** Female BALB/c mice were immunized three times with thyroid stimulating hormone receptor A-subunit encoded by adenovirus to establish a Graves’disease *** different doses of DHT or a matching placebo were administered by implantation of slow-release pellets a week before the first *** weeks after the third immunization,the mice were euthanatized,and then the spleen and thymus were *** thyroxine and free thyroxine levels in serum of mice were detected using a radioimmunoassay ***-time polymerase chain reaction was performed to estimate the expression of costimulatory molecules in lymphocytes from the spleen and *** cytometry was used to analyze the percentage of CD4^+T cells in splenic *** data were compared with unpaired *** between two variables was analyzed using Analysis of *** Treatment with DHT can dramatically reduce total thyroxine and free thyroxine *** expression of programmed death-1 was found in the spleen of Graves’disease mice receiving 5 mg of DHT treatment(0.635±0.296 vs.0.327±0.212;t=2.714,P=0.014),similarly,T-cell immunoglobulin domain and mucin domain 3(TIM-3)in both the spleen(1.004±0.338 vs.0.646±0.314;t=2.205,P=0.022)and the thymus(0.263±0.127 vs.0.120±0.076;t=3.221,P=0.004)also increased after 5 mg of DHT treatment compared with the parallel placebo model ***,the percentage of CD4^+T cells declined in the splenic lymphocytes of Graves’disease mice treated with 5 mg of DHT(19.90%

关键词： Graves’disease 5α-dihydrotestosterone costimulatory molecules inhibitory molecules

CD16+ Cells and costimulatory molecules of Lymphocyte Activation Present inside Human Kidney Grafts and in Blood Circulation

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Open Journal of Nephrology 2021年第1期11卷 93-113页

作者： Paula D. P. Xavier José G. G. Oliveira Instituto Português do Sangue e da Transplantaç ã o-área Transplantaç ã o Porto Portugal GCCT Centro Hospitalar Universitário S. Jo&#227 o Porto Portugal CINTESIS FMUP Porto Portugal

Background: We studied the expression of important costimulatory molecules of lymphocyte activation and the presence of CD16+ cells on aspiration biopsies of kidney transplants, measured three soluble factors and when indicated tested their robustness in diagnosing acute rejection. Methods: Fine-needle aspiration biopsies were performed either on days seven or 14 - 30 post-transplantation among stable kidney transplants and on the day of acute rejection diagnosis, while a sample of peripheral blood was collected simultaneously. The cyto preparations were studied by the enzymatic avidin biotin complex staining. The immunocytochemistry was directed to CD16, CD28, CD152, ICOS, CD40, CD154, CD26 and CD27. We performed the analysis in the peripheral blood by ELISA for soluble(s) CD16, CD26, and CD154. Results: The group of acute rejection cases showed a significant up-regulated expression of CD16, CD26, ICOS and CD40 as compared to the group of stable cases. Both sCD16 and sCD154 were significantly higher in the blood samples of the group with acute rejection. Thymoglobulin down-regulated CD154 and sCD16. CD16, CD26 and ICOS exhibited very high sensitivity and specificity for acute rejection diagnosis. Conclusions: The presence of CD16

关键词： Kidney Transplants Aspiration Biopsies costimulatory molecules CD16+ Cells

Cloning and Identification of Two Novel Splice Variants of Human PD-L2

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Acta Biochimica et Biophysica Sinica 2004年第4期36卷 284-289页

作者： Xian-Hui HE#*,Yi LIU&#,Li-Hui XU1, and Yao-Ying ZENG* Key Laboratory of Tissue Transplantation and Immunology, Ji’nan University, Ministry of Education, 601 Huangpu Road West, Guangzhou 510632, China 1Institute of Bioengineering, Ji’nan University, 601 Huangpu Road West, Guangzhou 510632, China Key Laboratory of Tissue Transplantation and Immunology Ji'nan University Ministry of Education601 Huangpu Road West Guangzhou 510632 China Institute of Bioengineering Ji'nan University601 Huangpu Road West Guangzhou 510632 China

PD-L2, a newly identified member of B7 family, plays a role in down-regulating T cell responses. The common PD-L2 mRNA (type I) is the splicing product containing all 6 exons. We report here the identification of two human PD-L2 splice variants in activated leukocytes. One splice variant (type II) is generated through splicing out exon 3 encoding Igconstant-like domain; it retains all other regions without a frame shift. The other variant (type III) is created by splicing out exon 3 to an alternative acceptor site 5 bp downstream of the canonical acceptor site, leading to a frame shift. Consequently, the translated protein should be a soluble form. Furthermore, type I isoform is expressed on the plasma surface whereas type II isoform showed a pattern of intracellular membrane distribution in the transiently transfected K562 cells. In addition, the expression patterns of PD-L2 splice variants are variable in different individuals and distinct cellular status. These results suggest that PD-L2 expression may be controlled by posttranscriptional regula- tion through alternative splicing, and modulation of PD-L2 isoform expression may influence the outcome of immune response.

关键词： costimulatory molecules PD-L2 splice variant leukocytes

A dimeric structure of PD-L1: functional units or evolutionary relics?

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Protein & Cell 2010年第2期1卷 153-160页

作者： Yong Chen Peipei Liu Feng Gao Hao Cheng Jianxun Qi George F.Gao CAS Key Laboratory of Pathogenic Microbiology and Immunology Institute of MicrobiologyChinese Academy of Sciences(CASPMI)Beijing 100101China College of Life Sciences Graduate UniversityChinese Academy of SciencesBeijing 100049China Institute of Biophysics Chinese Academy of SciencesBeijing 100101China China-Japan Joint Laboratory of Molecular Immunology and Molecular Microbiology Institute of MicrobiologyChinese Academy of SciencesBeijing 100101China

PD-L1 is a member of the B7 protein family,most of whose members so far were identified as dimers in a solution and crystalline state,either complexed or uncomplexed with their ligand(s).The binding of PD-L1 with its receptor PD-1(CD279)delivers an inhibitory signal regulating the T cell *** with the Garboczi group,we successfully solved another structure of human PD-L1(hPD-L1).Our protein crystallized in the space group of C222_(1) with two hPD-L1 molecules per asymmetric *** comparison of reported B7 structures,we have found some intrinsic factors involved in the interaction of these two *** on these results,we tend to believe this uncomplexed hPD-L1 structure demonstrated its potential dimeric state in solution,althougt it could just be an evolutionary relic,too weak to be detected under present technology,or still a functional unit deserved our attentions.

关键词： PD-L1 crystal structure dimer costimulatory molecules B7 family

Gene Therapy of Cancer:Induction of Anti-Tumor Immunity

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Cellular & Molecular Immunology 2004年第2期1卷 105-111页

作者： Jesus Prieto Division

Many malignancies lack satisfactory treatment and new therapeutic options are urgently *** therapy is a new modality to treat both inherited and acquired diseases based on the transfer of genetic material to the *** gene therapy strategies against cancers have been developed.A considerable number of preclinical studies indicate that a great variety of cancers are amenable to gene *** these strategies, induction of anti-tumor immunity is the most promising *** therapy with cytokines has reached unprecedented success in preclinical models of *** rather than additive effects have been demonstrated by combination of gene transfer of cytokines/chemokines,costimulatory molecules or adoptive cell *** progress in vector technology and in imaging techniques allowing in vivo assessment of gene expression will facilitate the development of clinical applications of gene therapy,a procedure which may have a notorious impact in the management of cancers lacking effective *** & Molecular Immunology.2004;1(2):105-111.

关键词： gene therapy anti-tumor immunity cytokines costimulatory molecules dendritic cell

Identification of a novel splice variant of human PD-L1 mRNA encoding an isoform-lacking Igv-like domain

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Acta Pharmacologica Sinica 2005年第4期26卷 462-468页

作者： Xian-hui HE~2 Li-hui XU Yi LIU~3 Key Laboratory of Ministry of Education for Tissue Transplantation and Immunology,Ji-nan University,Guangzhou 510632,China Key Laboratory of Ministry of Education for Tissue Transplantation and Immunology Ji-nan University Guangzhou China

Aim:To investigate the expression and regulation of PD-I ligand 1(PD-L1)inperipheral blood mononuclear cells(PBMC).Methods:The cDNA encoding hu-man PD-L1 precursor was cloned from the total RNA extracted from the restingand phorbol dibutyrate plus ionomycin-or phytohemagglutinin-activated PBMC,by reverse transcription polymerase chain reaction(RT-PCR),and independentclones were sequenced and *** expression and subcellular localizationwere examined in transiently transfected *** PD-L1 gene expression indifferent PBMC was also analyzed by ***:A novel human PD-LIsplice variant was identified from the activated *** was generated by splic-ing out exon 2 encoding an immunoglobulin variable domain(Igv)-like domain butretaining all other exons without a ***,the putative trans-lated protein contained all other domains including the transmembrane regionexcept for the Igv-like ***,the conventional isoform was ex-pressed on the plasma surface whereas the novel isoform showed a pattern ofintracellular membrane distribution in transiently transfected K562 *** addition,the expression pattern of the PD-L1 splice variant was variable in different indi-viduals and in different cellular ***:PD-L1 expression may beregulated at the posttranscriptional level through alternative splicing,and modu-lation of the PD-L1 isoform expression may influence the outcome of specificimmune responses in the peripheral tissues.

关键词： costimulatory molecules PD-L1 RNA splice sites subcellular localization

IMMUNOLOGICAL CHARACTERISTICS OF THE LEUKEMIA CELLS TRANSFECTED WITH ONCOSTATIN M GENE BY RECOMBINANT ADENOVIRUS

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Chinese Journal of Cancer Research 1997年第4期9卷 40-44页

作者：王全兴曹雪涛弭静章卫平

In the present study, FBL3 murine erythroleukemia cells were transfected with human OSM(hOSM) gene by recombinant adenovirus, then the immunological properties of hOSM genetransfected FBL3 cells(FBL3OSM+) were investigated. 4 hours after transfection with hOSM gene, hOSM could be detected in the supernatant of FBL3OSM+ cells and hOSM secretion peaked at 24 h. The proliferation of FBL3OSM+ cells was inhibited markedly. The clonal formation of FBL3OSM+ cells was suppressed more obviously in comparison with wildtype FBL3 cells when analysed in clonal argar culture. Flow cytometry analysis showed that FBL3OSM+ cells expressed higher levels of Fas protein, B7 and ICAM1 ***3OSM+ cells also expressed higher level of MHC class I molecules(H2Kb) but remained unchanged in expression of MHC class II molecules (Ia). CD14, which is a specific marker of monocyte/macrophage and not expressed on the wildtype FBL3 cells, was also detected on the surface of FBL3OSM+ cells. The results suggested that OSM gene transfer could increase the immunogenicity of FBL3 cells and promote their differentiation into macrophagelike cells. The data outline a promising approach to OSM gene therapy of leukemia mediated by recombinant adenovirus.

关键词： Oncostatin M Gene transfer Erythroleukemia Immunogenicity costimulatory molecules CD14.

Effects of vasoactive intestinal peptide on phenotypic and functional maturation of dendritic cells

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Effects of vasoactive intestinal peptide on phenotypic and f...

Thymic B cells promote regulatory T cells development rather than negative selection in the thymus

第十七次全国中西医结合肝病学术会议

作者： Jie Lu~a Ming-Hua Zheng~a Jie Yan~b Yong-Ping Chen~(a,§), Jian-Ping Pan~(b,§) a Department of Infectious and Liver Diseases, First Affiliated Hospital, Wenzhou Medical College, Wenzhou 323000, P R. China b Department of Microbiology and Parasitology, Zhejiang University School of Medicine, Hangzhou 310058, P R. China

The present study was designed to investigate the effects of vasoactive intestinal peptide (VIP) on differentiation, maturation of dendritic cells (DCs) in vitro. DCs were derived from the murine bone marrow hemopoietic progenitor cells by culturing in RPMI 1640 complete medium supplemented with GM-CSF and IL-4 in the presence or absence of various concentrations of vasoactive intestinal peptide (VIP) and lipopolysaccharide (LPS) The phenotype of DCs was analyzed by flow cytometry. Mixed leukocyte reaction (MLR) was employed to measure the capacity of DC to stimulate the allogeneic T cells. IL-12p70 secretion by DC was examined by ELISA. In the absence of LPS, VIP, in a dose dependent manner, up-regulated the expression of CDS0, CD86, CD54 and CD40, but down-regulated the expression of MHC class Ⅱ molecule (Ia). In the presence of LPS, VIP also dose dependently up-regulated the expression of CD80, CD86, CD54 and CD40, and down-regulated the expression of Ia. The capacity to stimulate alloreactive T cells and the production of IL-12p70 by DC were significantly augmented by VIP when compared with VIP-untreated DCs. These data suggest that VIP could promote the phenotypic and functional maturation of DCs, hereby regulating the type and outcome of the conducting immune response.

关键词： Dendritic cells Mixed leukocyte reaction IL-12 costimulatory molecules Vasoactive intestinal peptide

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Thymic B cells promote regulatory T cells development rather...