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

Jennifer L Gardell,David C Parker,Jean Kanellopoulos

doi:10.1371/journal.pone.0186573

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.

Highlights

B cells act as antigen-specific antigen-presenting cells (APCs) to solicit help from helper T cells (Th cells) in the antibody response [1]
To determine whether this difference was owing to culture in high concentrations of IL-4 during polarization of Th2 cells in vitro or truly owing to a difference between Th subsets, we used planar lipid bilayers containing fluorescent ICAM-1 and peptide-loaded MHC molecules to compare immunological synapses generated by Th2 cells that received either IL-4 or anti-IL-4 during secondary stimulation
This finding enabled us to compare the delivery of CD40 ligand (CD40L) by the two helper T cell subsets with distinct immunological synapse structures

Summary

Introduction

B cells act as antigen-specific antigen-presenting cells (APCs) to solicit help from helper T cells (Th cells) in the antibody response [1]. T cells deliver help in the form of the membrane bound cytokine, CD40L, and other cytokines to the B cells. The CD40L/CD40 interaction is required for the T cell-dependent antibody response. In CD40Lor CD40-deficient mice or after injection of anti-CD40L antibody, antibody formation is suppressed, and germinal centers do not develop [2, 3]. Due to the essential nature of this cytokine in development of adaptive immunity, it is important to determine how this cytokine is delivered in an antigen-specific manner. Targeted delivery of CD40L by helper T cells could limit

Methods

Results

Conclusion