The bullseye synapse formed between CD4+ T-cell and staphylococcal enterotoxin B-pulsed dendritic cell is a suppressive synapse in T-cell response

Immunol Cell Biol. 2015 Jan;93(1):99-110. doi: 10.1038/icb.2014.76. Epub 2014 Oct 7.

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.

MeSH terms

  • Animals
  • CTLA-4 Antigen / genetics
  • CTLA-4 Antigen / immunology
  • Calcium / immunology
  • Calcium / metabolism
  • Cell Communication
  • Dendritic Cells / cytology
  • Dendritic Cells / drug effects
  • Dendritic Cells / immunology*
  • Enterotoxins / pharmacology*
  • Female
  • Gene Expression Regulation
  • Immunological Synapses / chemistry*
  • Immunological Synapses / drug effects
  • Intercellular Adhesion Molecule-1 / immunology
  • Intercellular Adhesion Molecule-1 / metabolism*
  • Lymphocyte Activation
  • Lymphocyte Function-Associated Antigen-1 / immunology
  • Lymphocyte Function-Associated Antigen-1 / metabolism*
  • Mice
  • Mice, Inbred C57BL
  • Protein Binding
  • Receptors, Antigen, T-Cell / immunology
  • Receptors, Antigen, T-Cell / metabolism*
  • Signal Transduction
  • T-Lymphocytes, Regulatory / cytology
  • T-Lymphocytes, Regulatory / drug effects
  • T-Lymphocytes, Regulatory / immunology*

Substances

  • CTLA-4 Antigen
  • Enterotoxins
  • Lymphocyte Function-Associated Antigen-1
  • Receptors, Antigen, T-Cell
  • Intercellular Adhesion Molecule-1
  • enterotoxin B, staphylococcal
  • Calcium