We have already introduced the fact that there are abundant intraepithelial lymphocytes (IELs) present in intestine. In the healthy small intestine, there are 10–15 lymphocytes for every 100 epithelial cells, making the IELs one of the single largest populations of lymphocytes in the body (Fig. 12.13). More than 90% of the IELs in the small intestine are T cells, and around 80% of these carry CD8, in complete contrast to the lymphocytes in the lamina propria. IELs are also present in the large intestine, although there are fewer of them relative to the number of epithelial cells and the proportion of CD4 T cells is greater than in the small intestine.
Like the lymphocytes in the lamina propria, most IELs have an activated appearance even in the absence of infection by a pathogen, and they contain intracellular granules containing perforin and granzymes, like those in conventional effector CD8 cytotoxic T cells. However, the T-cell receptors of most CD8 IELs show evidence of oligoclonality, with restricted use of V(D)J gene segments, an indication that they may expand locally in response to a relatively small number of antigens. The IELs of the small intestine express the chemokine receptor CCR9, and the αE:β7 integrin (CD103), which interacts with E-cadherin expressed on epithelial cells and assists their retention in the epithelium (see Fig.12.9).
Fig.12.13 Intraepithelial lymphocytes. The epithelium of the are CD8 T cells. Magnification ×400. The electron micrograph on small intestine contains a large population of lymphocytes known the right shows that the IELs lie between epithelial cells (EC) on the as intraepithelial lymphocytes (IELs; left panel). The micrograph in basement membrane (BM) separating the lamina propria (LP) from the center is of a section through human small intestine in which the epithelium. One IEL can be seen having crossed the basement CD8 T cells have been stained brown with a peroxidase‑labeled membrane into the epithelium, leaving a trail of cytoplasm in its monoclonal antibody. Most of the lymphocytes in the epithelium wake. Magnification ×8000.
There are two main subsets of CD8 intraepithelial T cells—type a (‘inducible’) and type b (‘natural’)—identified based on which form of CD8 is expressed. The relative proportions of the subsets vary with age, strain (in mice), and number of bacteria in the intestine. Type a (inducible) IELs express α:β T-cell receptors and the CD8α:β heterodimer. They are derived from naive CD8 T cells that were activated by antigen in the Peyer’s patches or mesenteric lymph nodes, and they function as conventional class I MHC-restricted cytotoxic T cells, killing virus-infected cells, for example (Fig. 12.14, top panels). They also secrete effector cytokines such as IFN-γ.