Despite disorganized synapse structure, Th2 cells maintain directional delivery of CD40L to antigen-presenting B cells

PLoS One. 2017 Oct 12;12(10):e0186573. doi: 10.1371/journal.pone.0186573. eCollection 2017.

Abstract

Upon recognition of peptide displayed on MHC molecules, Th1 and Th2 cells form distinct immunological synapse structures. Th1 cells have a bull's eye synapse structure with TCR/ MHC-peptide interactions occurring central to a ring of adhesion molecules, while Th2 cells have a multifocal synapse with small clusters of TCR/MHC interactions throughout the area of T cell/antigen-presenting cell interaction. In this study, we investigated whether this structural difference in the immunological synapse affects delivery of T cell help. The immunological synapse is thought to ensure antigen-specific delivery of cytolytic granules and killing of target cells by NK cells and cytolytic T cells. In helper T cells, it has been proposed that the immunological synapse may direct delivery of other effector molecules including cytokines. CD40 ligand (CD40L) is a membrane-bound cytokine essential for antigen-specific T cell help for B cells in the antibody response. We incubated Th1 and Th2 cells overnight with a mixture of antigen-presenting and bystander B cells, and the delivery of CD40L to B cells and subsequent B cell responses were compared. Despite distinct immunological synapse structures, Th1 and Th2 cell do not differ in their ability to deliver CD40L and T cell help in an antigen-specific fashion, or in their susceptibility to inhibition of help by a blocking anti-CD40L antibody.

MeSH terms

  • Animals
  • Antibodies / immunology
  • Antibodies / pharmacology
  • Antigen-Presenting Cells / cytology
  • Antigen-Presenting Cells / metabolism*
  • B-Lymphocytes / immunology
  • B-Lymphocytes / metabolism*
  • CD40 Antigens / deficiency
  • CD40 Antigens / genetics
  • CD40 Ligand / genetics
  • CD40 Ligand / immunology
  • CD40 Ligand / metabolism*
  • Cyclosporine / pharmacology
  • Female
  • Immunological Synapses / chemistry
  • Immunological Synapses / drug effects
  • Immunological Synapses / immunology
  • Interleukin-4 / immunology
  • Lymphocyte Activation / drug effects
  • Male
  • Mice
  • Mice, Knockout
  • Mice, Transgenic
  • Microscopy, Confocal
  • Synapses / chemistry*
  • Synapses / metabolism
  • Th1 Cells / cytology
  • Th1 Cells / metabolism
  • Th2 Cells / cytology
  • Th2 Cells / metabolism*

Substances

  • Antibodies
  • CD40 Antigens
  • CD40 Ligand
  • Interleukin-4
  • Cyclosporine