Intraepithelial lymphocytes (IELs) are small, round mononuclear white blood cells, which reside in the paracellular space between epithelial cells. They are found in the skin and within the epithelial layer that lines the intestine, the biliary tract, the oral cavity, the upper respiratory tract and lungs and the reproductive tract. IELs constitute a heterogeneous population of T lymphocytes that express an αβ or γδ T cell receptor (TCR) on their cell surface. IELs characteristically display an antigen‐experienced phenotype; they vary in their major histocompatibility complex restriction and TCR antigen specificity. All these characteristics are common features of the IEL pool with some variations depending on the tissue where they reside. The largest population of IELs resides within the epithelium of the small intestine, where they function to preserve the integrity of the mucosal barrier by protecting the epithelium against pathogen‐ or immune‐induced pathology.
Key Concepts:
The lymphocytes located in the epithelium are exposed to self, pathogenic and harmless nonself antigens.
The T‐cell populations that reside within the small intestinal epithelium are the most significant in number and the most diverse of all lymphocyte populations in the body.
The T‐cell populations that reside within the epithelium contain unconventional subpopulations such as the CD8αα TCRαβ
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IELs.
Self‐specific CD8αα TCRαβ
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IELs acquire their functional antigen‐experienced differentiation during a specific agonist selection process in the thymus.
IELs function to protect the epithelium against pathogen‐induced as well as immune‐induced pathology.