Enteric glia promotes the survival of CD4 and CD8 T cells in plexitis: a new player in Crohn's disease recurrence?

Abstract

The accumulation of immune cells in and around enteric ganglia, called plexitis, is associated with postoperative recurrence in Crohn's disease. Interaction between T cells and enteric glia is increased at the proximal resection margin in patients with Crohn's disease who suffer from postoperative recurrence. However, little is known about the T cells that interact with enteric glia and contribute to the formation of plexitis. In this work, the number of CD4 and CD8 T cells interacting with enteric glia was quantified in sections of the proximal (ileal) resection margin of patients with Crohn's disease, and in cocultures prepared with rat and human enteric glia. The molecules implicated in these interactions were investigated, as well as the impact of enteric glia on T cell survival. Analyses indicated that both CD4 and CD8 cells were present and in contact with enteric glia in plexitis in patients with Crohn's disease. In vitro studies demonstrated that the adhesion of both human and rat CD4 and CD8 cells to enteric glia was increased after pretreatment of the glial cells with IL1β/TNFα, and that this adhesion was lymphocyte function-associated antigen 1 (LFA-1)-dependent. The interactions between T cells and enteric glia increased the survival of CD4 and CD8 T cells in an ICAM-1/LFA-1-independent manner. In conclusion, both CD4 and CD8 T lymphocytes are present and in contact with enteric glia in plexitis. The in vitro studies demonstrate that they adhere to human and rat enteric glia through LFA-1 and show that interactions with enteric glia promote their survival, independently of LFA-1.NEW & NOTEWORTHY Both CD4 and CD8 T cells adhere to enteric glial cells in patients with Crohn's disease, contributing to the development of plexitis associated with postoperative recurrence. The adhesion of CD4 and CD8 T cells to enteric glial cells is dependent on ICAM-1/LFA-1. Enteric glial cells promote the survival of CD4 and CD8 T cells independently of ICAM-1/LFA-1.

Keywords: Crohn’s disease; T lymphocyte; enteric glial cell; enteric nervous system; plexitis.