Mucosal T cells in gut homeostasis and inflammation

Figure 1. Intestinal T-cell subsets. The lamina propria and epithelium of the intestine harbor diverse populations of T cells. Conventional or 'type a' mucosal T cells that have matured in the thymus along the conventional selection pathway migrate, after antigen priming in the mesenteric lymph nodes, mainly to the lamina propria but also the epithelium. Upon entry into the epithelium, these cells often coexpress the CD8αα homodimer. Most intraepithelial lymphocytes (IELs), however, belong to two subsets of unconventional or 'type b' mucosal T-cell populations: the TCRgD ⁺ CD8αα⁺ IELs that are thymus derived and develop along the double-negative pathway and the TCRαb⁺ CD8αα⁺ IELs that have matured and differentiated in the thymus along the agonist-selection pathway. Both subsets migrate as antigen-experienced directly to the intestine where the majority of cells upregulate CD8αα, while some remain double negative. DN: Double negative; TCR: T-cell receptor.
(Figure omitted. See article PDF.)

Figure 2. Mucosal T-cell regulation and activation. The functionally diverse T-cell populations of the intestine that are shaped by the gut environment are important players in sustaining the delicate immune balance between activation and regulation. The CD8αα ⁺ IELs of the intestine play a crucial role in protecting the mucosal barrier. They are involved in maintaining and restoring barrier homeostasis by stimulating IEC turnover. Upon pathogen entry, rapid activation and high cytolytic activity of the CD8αb ⁺ IELs contribute to the prevention of pathogen spreading by killing infected IECs. The activation of IELs is highly controlled through the expression of inhibitory receptors that may alter the threshold for activation. In some conditions, such as celiac disease, activation of CD8αb ⁺ cytotoxic T lymphocytes is associated with epithelial damage. In the lamina propria (LP), all classical CD4⁺ Th subtypes are present. Under the influence of IECs and IELs, LP DCs acquire the ability to produce RA, thereby inducing gut-homing receptors during CD4 T-cell priming in the mLNs. The LP of the gut is enriched with both Foxp3⁺ Tregs and Th17 cells. Gut-derived CD103⁺ DCs favor the conversion of Foxp3⁺ iTregs in a RA- and TGF-b-mediated fashion, whereas activated DCs promote the differentiation of IL-17-producing Th17 cells via a combination of IL-6 and TGF-b. This pro- and anti-inflammatory immune deviation of...