Intestinal intraepithelial lymphocytes: Maintainers of intestinal immune tolerance and regulators of intestinal immunity

Intestinal immune tolerance is essential for the immune system, as it prevents abnormal immune responses to large quantities of antigens from the intestinal lumen, such as antigens from commensal microorganisms, and avoids self‐injury. Intestinal intraepithelial lymphocytes (IELs), a special group of mucosal T lymphocytes, play a significant role in intestinal immune tolerance. To accomplish this, IELs exhibit a high threshold of activation and low reactivity to most antigens from the intestinal lumen. In particular, CD8αα(+)TCRαβ(+) IELs, TCRγδ(+) IELs, and CD4(+)CD8αα(+) IELs show great potential for maintaining intestinal immune tolerance and regulating intestinal immunity. However, if the intestinal microenvironment becomes abnormal or intestinal tolerance is broken, IELs may be activated abnormally and become pathogenic.