title: The bullseye synapse formed between CD4+ T-cell and staphylococcal enterotoxin B-pulsed dendritic cell is a suppressive synapse in T-cell response.
abstract: The immunological synapse (IS) is a supermolecular activation cluster formed between T cells and antigen-presenting cells. Although diverse IS structures have been reported, the function of the IS in T-cell activation remains unclear. Here, we found that the bullseye IS, one of IS types at the interface of CD4(+) T cells and staphylococcal enterotoxin B-pulsed dendritic cells, suppressed CD4(+) T-cell activation, whereas multifocal IS, another synapse type, stimulated CD4(+) T-cell activation. Consistent with these results, bullseye IS formation was accompanied by a low-level calcium response in T cells and a loss of T-cell receptor signalling molecules from the synapse, whereas multifocal IS exhibited the opposite. Furthermore, we found that CD4(+)CD25(+) regulatory T cells (T(regs)) more efficiently formed bullseye IS and promoted bullseye IS formation in CD4(+) CD25(-) T cells. Cytotoxic T-lymphocyte antigen-4 (CTLA-4), an inhibitory molecule expressed continuously on T(regs), was localised in bullseye IS. Moreover, blocking CTLA-4 reduced the percentage of bullseye IS formation and promoted T-cell activation. Our data thus indicate that bullseye IS formation is mediated by CTLA-4, and may negatively control T-cell activation as a suppressive synapse.
authors.affiliation: 1] Department of Immunology and Key Laboratory of Medical Molecular Virology of MOE/MOH, School of Basic Medical Sciences, Fudan University, Shanghai 200032, China [2] Biotherapy Research Centre, Fudan University, Shanghai 200032, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Lin
authors.affiliation: State Key Laboratory of Oncogenes and Related Genes, Shanghai Cancer Institute, School of Biomedical Engineering, Shanghai Jiao Tong University, Shanghai 200030, China.
authors.forename: Zhichao
authors.initials: Z
authors.lastname: Fan
authors.affiliation: State Key Laboratory of Oncogenes and Related Genes, Shanghai Cancer Institute, School of Biomedical Engineering, Shanghai Jiao Tong University, Shanghai 200030, China.
authors.forename: Yuanzhen
authors.initials: Y
authors.lastname: Suo
authors.affiliation: 1] Department of Immunology and Key Laboratory of Medical Molecular Virology of MOE/MOH, School of Basic Medical Sciences, Fudan University, Shanghai 200032, China [2] Biotherapy Research Centre, Fudan University, Shanghai 200032, China.
authors.forename: Yuting
authors.initials: Y
authors.lastname: Deng
authors.affiliation: 1] Department of Immunology and Key Laboratory of Medical Molecular Virology of MOE/MOH, School of Basic Medical Sciences, Fudan University, Shanghai 200032, China [2] Biotherapy Research Centre, Fudan University, Shanghai 200032, China.
authors.forename: Min
authors.initials: M
authors.lastname: Zhang
authors.affiliation: 1] Department of Immunology and Key Laboratory of Medical Molecular Virology of MOE/MOH, School of Basic Medical Sciences, Fudan University, Shanghai 200032, China [2] Biotherapy Research Centre, Fudan University, Shanghai 200032, China.
authors.forename: Jiyang
authors.initials: J
authors.lastname: Wang
authors.affiliation: State Key Laboratory of Oncogenes and Related Genes, Shanghai Cancer Institute, School of Biomedical Engineering, Shanghai Jiao Tong University, Shanghai 200030, China.
authors.forename: Xunbin
authors.initials: X
authors.lastname: Wei
authors.affiliation: 1] Department of Immunology and Key Laboratory of Medical Molecular Virology of MOE/MOH, School of Basic Medical Sciences, Fudan University, Shanghai 200032, China [2] Biotherapy Research Centre, Fudan University, Shanghai 200032, China.
authors.forename: Yiwei
authors.initials: Y
authors.lastname: Chu
mesh_terms: D000818:Animals; D060908:CTLA-4 Antigen / Q000235:genetics / Q000276:immunology; D002118:Calcium / Q000276:immunology / Q000378:metabolism; D002450:Cell Communication; D003713:Dendritic Cells / Q000166:cytology / Q000187:drug effects / Q000276:immunology*; D004768:Enterotoxins / Q000494:pharmacology*; D005260:Female; D005786:Gene Expression Regulation; D054992:Immunological Synapses / Q000737:chemistry* / Q000187:drug effects; D018799:Intercellular Adhesion Molecule-1 / Q000276:immunology / Q000378:metabolism*; D008213:Lymphocyte Activation; D016169:Lymphocyte Function-Associated Antigen-1 / Q000276:immunology / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D011485:Protein Binding; D011948:Receptors, Antigen, T-Cell / Q000276:immunology / Q000378:metabolism*; D015398:Signal Transduction; D050378:T-Lymphocytes, Regulatory / Q000166:cytology / Q000187:drug effects / Q000276:immunology*
chemical_list: D060908:CTLA-4 Antigen; D004768:Enterotoxins; D016169:Lymphocyte Function-Associated Antigen-1; D011948:Receptors, Antigen, T-Cell; D018799:Intercellular Adhesion Molecule-1; C031818:enterotoxin B, staphylococcal; D002118:Calcium