Fig. 12.8 Priming of naive T cells and the redistribution of effector T cells in the intestinal immune system. Naive T cells carry the chemokine receptor CCR7 and L‑selectin, which direct their entry into Peyer’s patches via high endothelial venules (HEVs). In the T‑cell area they encounter antigen that has been transported into the lymphoid tissue by M cells and is presented by local dendritic cells. During activation, and under the selective control of gut‑derived dendritic cells, the T cells lose L‑selectin and acquire the chemokine receptor CCR9 and the integrin α4:β7. After activation, but before full differentiation, the primed T cells exit from the Peyer’s patch via the draining lymphatics, passing through the mesenteric lymph node to enter the thoracic duct. The thoracic duct empties into the bloodstream, delivering the activated T cells back to the wall of the small intestine. Here T cells bearing CCR9 and α4:β7 are attracted specifically to leave the bloodstream and enter the lamina propria of the villus.
bloodvessellaminapropriaCCR10CCR9MAdCAM-1˜4:°7Gut-homing effector T cells bind MAdCAM-1 on endothelium largeintestinesmallintestineendotheliumepitheliumCCL25E-cadherin˜E:°7CCL28Gut epithelial cells express chemokines specifc for gut-homing T cells
Fig. 12.9 Molecular control of intestine-specific homing of lymphocytes.
α:β form of CD8 or the CD8α:α homodimer, which may act to dampen T-cell activation. These IELs express CCR9 and the integrin αE:β7 (CD103), which binds to E-cadherin on epithelial cells (Fig. 12.9). By contrast, in the lamina propria it is CD4 T cells that predominate.
The healthy intestinal mucosa therefore displays many characteristics of a chronic inflammatory response—namely, the presence of numerous effector lymphocytes and other leukocytes in the tissues. The presence of such large numbers of effector cells would be unusual for a healthy nonlymphoid tissue, but in the gut does not necessarily signify infection. Rather, it is the local response to the myriad innocuous antigens normally present at mucosal surfaces, and is essential for maintaining the beneficial symbiosis between host and microbiota. It involves a balanced generation of effector and regulatory T cells, but, when required, can be refocused to produce a full adaptive immune response to invading pathogens.
12-5 The circulation of lymphocytes within the mucosal immune system is controlled by tissue-specific adhesion molecules and chemokine receptors.