Lymphocytes: Intraepithelial


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+ IELs.

  • Self‐specific CD8αα TCRαβ+ 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.

Keywords: γδ; T cell; αβ; CD8; Cytotoxic T cell; cytokine; agonist selection

Figure 1.

(a) Villi architecture of the small intestinal epithelium in mouse. Hematoxyline and Eosin staining. (b) T cells in the villi of normal human small intestine. Note the high density of T cells (intraepithelial lymphocytes) are basolaterally situated in the epithelial layer. Immunoperoxidase with anti‐CD3, original magnification×100.

Figure 2.

Schema summarising the differentiation of induced and natural IEL. CD4 and CD8αβ TCRab differentiate in the thymus through a CD4+ CD8αβ+ (DP) stage. CD4 and CD8αβ+ mature T cells leave the thymus to colonise peripheral lymphoid tissue where they stay as naïve T cells. Under antigenic stimulation they will differentiate into effector T cells and gain the capacity to migrate to the intestinal epithelium. CD8αα TCRαβ differentiate in the thymus through the CD4 CD8αβ CD8αα (TP) stage and later CD4 CD8αβ (DN) TCRαβ+. DN TCRαβ+ egress the thymus and reach the small intestine epithelium, where they express CD8αα under IL‐15 to become CD8αα TCRαβ IEL. Finally CD8αα TCRγδ IEL develop from CD4 CD8αβ (DN) precursors.

Figure 3.

Schematic representation of the recognition elements of human TCRγδ IEL and TCRαβ on the surface of normal and infected epithelial cells. In normal situation, natural TCRγδ IEL respond to stress signals and produce cytokines that result in the protection of the epithelium (including IEC growth and wound repair). Induced TCRαβ IEL has a crucial role in preventing pathogens from entering the intestinal barrier. They are responsible for IEC lysis through cytotoxic mechanism involving granzyme B and perforin as well as inflammatory cytokines (INFγ and TNFα).



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Further Reading

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Lambolez, Florence, Mayans, Sofia, and Cheroutre, Hilde(May 2013) Lymphocytes: Intraepithelial. In: eLS. John Wiley & Sons Ltd, Chichester. [doi: 10.1002/9780470015902.a0001197.pub3]