Regulatory T cells: peace keepers in the gut

Abstract

The mucosa-associated lymphoid tissue (MALT) has the task of protecting the host from pathogens while maintaining the integrity of the gut. Immune responses are tightly regulated such that there is tolerance of nonpathogenic bacteria as well as dietary antigens present in the intestinal lumen. The failure to control these responses leads to a disruption in tolerance, which has been proposed as one mechanism involved in the development of inflammatory bowel disease (IBD). Different mechanisms are involved in the control of immune responses in the intestinal tract, including active suppression by regulatory T cells. Distinct subsets of regulatory T cells coexist in the intestinal mucosa, which is a fertile environment for their growth. Most of these are defined by their phenotype and/or their ability to produce regulatory cytokines such as interleukin-10 and transforming growth factor-beta A lack of activation and/or expansion of regulatory cells could play a role in the uncontrolled inflammation seen in IBD. Regulatory T cells may be activated by cytokines, and their inductive phase may be antigen-driven. There are limited data relating to the true surface interactions regulating the activation of these cells. Most of the CD4 regulatory T cells (Tr1, Th3, and CD4 CD25+) are thought to interact with dendritic cells. Subsets of regulatory T cells (such as CD8 TrE cells) may recognize antigens presented by intestinal epithelial cells. A better understanding of the mechanisms by which these regulatory T cells are expanded and/or activated in the intestinal mucosa may provide clues as how to use them as a novel therapeutic tool in the treatment of patients with IBD.