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Keratinocytes costimulate naive human T cells via cd2: a potential target to prevent the development of proinflammatory Th1 cells in the skin

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Cellular & Molecular Immunology 2020年第4期17卷 380-394页

作者： Christian Orlik Daniel Deibel Johanna Küblbeck Emre Balta Sabina Ganskih Jüri Habicht Beate Niesler Jutta Schröder-Braunstein Knut Schäkel Guido Wabnitz Yvonne Samstag Institute of Immunology Section Molecular ImmunologyHeidelberg UniversityIm Neuenheimer Feld 30569120 HeidelbergGermany Institute of Human Genetics Department of Human Molecular Geneticsand nCounter Core FacilityHeidelberg UniversityIm Neuenheimer Feld 36669120 HeidelbergGermany Department of Dermatology Heidelberg UniversityIm Neuenheimer Feld 44069120 HeidelbergGermany

The interplay between keratinocytes and immune cells,especially T cells,plays an important role in the pathogenesis of chronic inflammatory skin *** psoriasis,keratinocytes attract T cells by releasing chemokines,while skin-infiltrating selfreactive T cells secrete proinflammatory cytokines,e.g.,IFN γand IL-17A,that cause epidermal ***,in chronic graftversus-host disease,allogenic IFN γ-producing Th1/Tc1 and IL-17-producing Th17/Tc17 cells are recruited by keratinocyte-derived chemokines and accumulate in the ***,whether keratinocytes act as nonprofessional antigen-presenting cells to directly activate naive human T cells in the epidermis remains ***,we demonstrate that under proinflammatory conditions,primary human keratinocytes indeed activate naive human T *** activation required cell contact and costimulatory signaling via cd58/cd2 and cd54/*** T cells costimulated by keratinocytes selectively differentiated into Th1 and Th17 *** particular,keratinocyte-initiated Th1 differentiation was dependent on costimulation through cd58/*** latter molecule initiated STAT1 signaling and IFN γproduction in T *** of T cells by keratinocytes resulting in Th1 and Th17 differentiation represents a new explanation for the local enrichment of Th1 and Th17 cells in the skin of patients with a chronic inflammatory skin ***,local interference with T cell–keratinocyte interactions may represent a novel strategy for the treatment of Th1 and Th17 cell-driven skin diseases.

关键词： keratinocytes inflammatory skin diseases psoriasis human T cells costimulation cd2 LFA-1 nonprofessional antigenpresenting cells Th1 cells Th17 cells

Detection of cd2 expression in chicken hematogenic embryo yolk sac lymphoid cells prior to thymus genesis

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Progress in Natural Science:Materials International 2008年第12期18卷 1589-1594页

作者： Dongyu Zhou~a Jigui Wang~b Weiquan Liu~b Rongxiu Liu~c Yuehu Pei~a a College of Traditional Chinese Materia Medica,Shenyang Pharmaceutical University,Shenyang 110016,China b College of Biological Sciences,China Agricultural University,Beijing 100094,China c Liaoning Tianhe Biotechnology Co.Ltd,Room 1203,100-1 Dongbinhe Road,Shenyang District,Shenyang 110016,China [a]College of Traditional Chinese Materia Medica Shenyang Pharmaceutical University Shenyang 110016 China [b]College of Biological Sciences China Agricultural University Beijing 100094 China [c]Liaoning Tianhe Biotechnology Co. Ltd Room 1203 100-1 Dongbinhe Road Shenyang District Shenyang 110016 China

Lymphoid mononuclear cells from chick embryos at stage 16 were collected prior to fetal liver and thymus genesis to study the dif- ferentiation and function of the hematogenic yolk sac and to detect whether cd2 occurs on the surface of lymphoid mononuclear cells. The phenotype and functional activity of the cell surface protein E receptor and the ultrastructure of embryonic E~+ cells were compared with those of mature T *** results indicate 99.36% homology between the E receptors of embryonic lymphocytes and mature T *** similarities,including molecular distribution,motivation,the ability to form an erythrocyte rosette,the structure of the receptor-ligand complex,and the conformation of the signal channel,were detected between embryonic lymphocytes and mature cd2-expressing T *** results indicate that cd2 is already expressed prior to fetal liver and thymus genesis and that its expression is not dependent on the thymic microenvironment.

关键词： cd2 Chicken embryo Hematogenic yolk sac

v-Fos transformation effector binds with cd2 cytoplasmic tail

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Chinese Science Bulletin 2006年第1期51卷 38-47页

作者： LI Ming ZHANG Weilun LIU Shilian LIU Yanxin ZHENG Dexian National Laboratory of Medical Molecular Biology Institute of Basic Medical Sciences Chinese Academy of Medical Sciences & Peking Union Medical College Beijing 100005 China

We previously reported that v-Fos transformation effector (Fte-1) is a novel cd2 binding protein identified by yeast two hybrid system. In the present study, we further characterize the molecular properties and biological activity of the Fte-1. In vitro interaction analysis by an IAsys Resonant Mirror Bio- sensor further demonstrated that Fte-1 interacts with cd2 specifically, and the dissociation constant (Kd) of Fte-1-cd2 is 10?7 mol. The molecular section analysis showed that protein kinase C (PKC) phos- phorylation site at Ser238 of Fte-1, as confirmed by in vitro phosphorylation, is essential for the specific in- teraction with cd2. Jurkat T cells transfected with expression vector encoding for EGFP-Fte-1 fusion protein showed that Fte-1 displays a clustering dis- tribution in the cells. Upon stimulation by cd2 mono- clonal antibody T11, Fte-1 lost the character of clus- tering distribution and translocation to the plasma membrane, which were disrupted by mutation of Fte-1 (Ser238Gly), suggesting that Fte-1 could be co-localized with cd2 on the membrane, and Fte-1 phosphorylation at Ser238 is a crucial factor in cd2-mediated interaction with Fte-1. Suppression of Fte-1 expression by small interference RNA (siRNA) diminished the susceptibility of Jurkat T cells to apoptosis triggered by phorbol 12-myristate 13-ace- tate (PMA) and ionomycin, indicating that the bio- logical function of Fte-1 may be involved in the regu- lation of activation and apoptosis of T cells. These results provide further evidence that Fte-1 is a novel binding protein of cd2, and may function as a down- stream molecule in the cd2-mediated events.

关键词：磷酸化 Fte-1 cd2 结合蛋白 PKC

Cloning and identification of a novel binding protein of cd2 cytoplasmic domain

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Chinese Science Bulletin 2000年第24期45卷 2263-2267页

作者： SHAO Yuan XIAO Sheng ZHAI Wenjing LI Dong LIU Yanxin LIU Shilian ZHENG Dexian State Key Laboratory of Experimental Hematology Institute of HematologyChinese Academy of Medical Sciences and Peking Union Medical CollegeTianjin 300020China State Key Laboratory of Medical Molecular Biology Institute of Basic Medical SciencesChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100005China

In order to understand why cd2 has a dual action of transduction of activation or apoptosis signals in T cells under different experimental conditions, we employed a yeast two-hybrid system to look for a binding protein of the cytoplasmic domain of cd2 which may be involved in this issue. A human T cell cdNA library was screened by a cdNA encoding the cytoplasmic domain of cd2 (Thr211-Gln336). The specificity of protein-protein interaction was verified by co-immunoprecipitation. The binding protein obtained, designated cd2cBP, was found to be homologous to v-fos transformation effector protein (Fte-1). As Fte-1 plays a role in cell transformation, growth, protein synthesis and protein-import into mitochondria, this result suggests that cd2cBP may be putatively involved in cd2-mediated signaling.

关键词： cd2 binding protein cytoplasmic domain yeast two-hybrid system signal transduction.

cd2 deficiency partially prevents small bowel inflammation and improves parasite control in murine Toxoplasma gondii infection

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World Journal of Gastroenterology 2007年第31期13卷 4207-4213页

作者： Nina N Pawlowski Daniela Struck Katja Grollich Anja A Kühl Martin Zeitz Oliver Liesenfeld Jrg C Hoffmann Medizinische Klinik I Charité-Universittsmedizin Berlin Campus Benjamin Franklin D12200 Berlin Germany Institut für Mikrobiologie und Hygiene Charité-Universittsmedizin Berlin Campus Benjamin Franklin D12203 Berlin Germany

To investigate whether bowel inflammation and/or parasite control is altered in the absence of the T cell adhesion molecule cd2.

关键词： cd2 IL-6 Ileitis Inflammatory bowel dis-ease Interferon-T Toxoplasma gondii

The Expression of cd2 in Chronic HBV Infection

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Cellular & Molecular Immunology 2008年第1期5卷 69-73页

作者： Jie Li Baotai Qi Ping Chen Linjing He Ping Wang Yuqiang Ji Ming Xie Department of Pathogenic Microbiology and Immunology Medical School of Xi＇an Jiaotong University Xi＇an 710061 China

It was previously reported that several kinds of intercellular adhesion molecules are closely related to chronic HBV infection. The complex of cd2 and cd58 plays an important role in enhancing the adhesion of T lymphocytes to target cells, and promoting hyperplasia and activation of T lymphocytes. In this study, we detected the level of cd2 expressed on the surface of PBMC, the expression level of cd2 mRNA in PBMC and the percentage of cd2 positive cells in PBMC of patients with chronic HBV infection and compared them with the expression level of normal controls. We also determined the level of serum HBV DNA from patients with chronic HBV infection and from normal controls. The clinical characteristics of hepatic function were tested as well. The results showed that the expression of cd2 significantly increased with the severity of chronic HBV infection, which suggested that cd2 might contribute to the hepatocyte damage in chronic HBV infection. Cellular ＆ Molecular Immunology.

关键词： chronic HBV infection cd2 RT-PCR

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v-fos转化效应因子是cd2胞内区新的结合蛋白

International Forum 2003 Academic Conference of Dermatology of the Integration of TCM with Western Medicine

作者： Liu Hui, Gu Jun, Guo Feng,et al Department of Dermatology , Changhai Hospital, Second Military Medical University , Shanghai 20043, China

In order to study the expression of innate immunal molecular cd35/cd59 on platelet and cd2 on peripheral blood lymphocytes in patients withpsoriasis, and find the possible role of it in the pathogenesis of psoriasis,we determined the expression level of cd35/cd59 on platelet and cd2 onperipheral blood lymphocytes in patients with psoriasis by FCM. The re-

关键词： Psoriasis Lymphocytes cd2 Platelet cd35 cd59 Innate immune Pathogenesis

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科学通报 2006年第2期51卷 152-160页

作者：李明张伟伦刘士廉刘彦信郑德先中国医学科学院/中国协和医科大学基础医学研究所医学分子生物学国家重点实验室北京100005

在以前的研究中,本实验室采用酵母双杂交技术,从人KT3T淋巴细胞cdNA文库中筛选到一个与cd2胞内区结合的新的蛋白分子,称为v-fos转化效因子(v-fostransformationeffector,Fte-1).本研究进一步分析鉴定了Fte-1与cd2相互作用的分子机制和Ft... 详细信息

在以前的研究中,本实验室采用酵母双杂交技术,从人KT3T淋巴细胞cdNA文库中筛选到一个与cd2胞内区结合的新的蛋白分子,称为v-fos转化效因子(v-fostransformationeffector,Fte-1).本研究进一步分析鉴定了Fte-1与cd2相互作用的分子机制和Fte-1的生物学功能.应用研究生物大分子相互作用的生物传感器分析了cd2胞内区与Fte-1结合特性和亲和力,表明二者确为特异性结合,其解离常数KD值为10?7mol/L;分子缺失突变和体外磷酸化实验结果表明,Fte-1可被蛋白激酶C(PKC)磷酸化,其磷酸化位点为Ser238;基因表达研究显示,在JurkatT淋巴细胞白血病细胞中Fte-1呈簇集性分布;cd2单克隆抗体T11刺激JurkatT淋巴细胞后,Fte-1这种簇集性分布特征消失,而趋向细胞膜,并与cd2共定位于细胞膜区域;Fte-1的PKC磷酸化位点Ser238突变为Gly238后,其与cd2分子的共定位能力丧失,表明Fte-1的Ser238的PKC磷酸化对Fte-1和cd2在T淋巴细胞内的结合起关键作用;使用Fte-1干扰RNA技术抑制Fte-1在JurkatT淋巴细胞中的表达,可抑制佛波酯(PMA)和离子霉素(ionomycin)引起的JurkatT淋巴细胞激活后凋亡,提示Fte-1参与了cd2对T淋巴细胞凋亡的调节.上述结果进一步确证Fte-1是cd2胞内区的特异结合蛋白,并可能参与了cd2介导的细胞凋亡信号传递.

关键词： vofos转化效因子 cd2 结合蛋白蛋白激酶C 磷酸化

人外周血淋巴细胞激活与cd2 mRNA 表达

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中国免疫学杂志 1992年第1期8卷 35-39页

作者：郭波郑德先许成素李晓露刘士廉中国医学科学院基础医学研究所北京100005 中国医学科学院阜外医院

对 PHA、抗 cd3单克隆抗体 RW2—8C8、胸腺肽、抗 cd2与抗 cd3等对人 T 淋巴细胞的增殖现象及动力学进行了观察,除抗 cd3与抗 cd2单抗联合应用为抑制效应外,前三者均呈正效应且动力学完全一致.在此基础上,应用反义 cd2mRNA 探针检测了 m... 详细信息

对 PHA、抗 cd3单克隆抗体 RW2—8C8、胸腺肽、抗 cd2与抗 cd3等对人 T 淋巴细胞的增殖现象及动力学进行了观察,除抗 cd3与抗 cd2单抗联合应用为抑制效应外,前三者均呈正效应且动力学完全一致.在此基础上,应用反义 cd2mRNA 探针检测了 mRNA 在激活24小时以后的变化,发现 T 细胞活化者均显示 mRNA 量呈上升;反之则不见变化或低于未激活 T 细胞对照组水平.本研究证明了小牛胸腺肽有激活 T 细胞和提高 mRNA 水平的作用,为首次报导.本文对上述在基因水平上观察的结果进行了讨论.

关键词： PHA cd2 cd2 mRNA T细胞激活外周血淋巴细胞