Patients with inflammatory bowel disease (IBD) reveal increased induction capacity of intracellular interferon-gamma (IFN-γ) in peripheral CD8+ lymphocytes co-cultured with intestinal epithelial cells

Abstract

SUMMARYIntestinal epithelial cells seem to play a key role during IBD. The network of cellular interactions between epithelial cells and lamina propria mononuclear cells is still incompletely understood. In the following co-culture model we investigated the influence of intestinal epithelial cells on cytokine expression of T cytotoxic and T helper cells from patients with IBD and healthy controls. Peripheral blood mononuclear cells (PBMC) were purified by a Ficoll±Hypaque gradient followed by coincubation with epithelial cells in multiwell cell culture insert plates in direct contact as well as separated by transwell filters. We used Caco-2 cells as well as freshly isolated colonic epithelia obtained from surgical specimens. Three-colour immunofluorescence flow cytometry was performed after collection, stimulation and staining of PBMC with anti-CD4, anti-

Regulation ofα1-proteinase inhibitor release by proinflammatory cytokines in human intestinal epithelial cells

“…+ lymphocytes from patients with IBD -even during inactive disease -was markedly up-regulated during co-culture with Caco-2 cells [36]. Healthy controls did not respond to the epithelial stimulus.…”

Breakdown in Repression of IFN-γ mRNA Leads to Accumulation of Self-Reactive Effector CD8+ T Cells

“…Breakdown in CD8 + T cell tolerance plays a major role in the development of type 1 diabetes and contributes to multiple sclerosis (1)(2)(3)(4). Expansion of autoreactive CD8 + effector T cells has also been associated with other autoimmune diseases, including pancreatitis, autoimmune gastritis, inflammatory bowel disease, and systemic lupus erythematosus (5)(6)(7)(8). Over the past few decades, we have gained considerable understanding about the cellular and molecular mechanisms that drive CD8 + effector T cell differentiation and clonal expansion during infection.…”

The CD40-CD40L Pathway Contributes to the Proinflammatory Function of Intestinal Epithelial Cells in Inflammatory Bowel Disease

“…In active IBD, IECs were shown to stimulate CD4 ϩ and CD8 ϩ effector T cells. 5,6 Therefore, CD40 might be involved in various proinflammatory functions of IECs in innate and adaptive immune responses. Further studies will have to address this issue.…”

“…IECs are known to be involved in the regulation of mucosal immune responses to luminal antigens. 3,4 They function as antigen presenting cells (APCs) to different subsets of T cells 3,[5][6][7] and moreover play a role in the innate immune response through secretion of a panel of cytokines and chemokines. 8 -11 In this regard IECs substantially contribute to the inflammatory processes in IBD by stimulating effector T cells and the release of interleukin (IL)-1, IL-6, IL-8, or tumor necrosis factor (TNF)-␣.…”