The entry of effector lymphocytes into the mucosa results from changes in their homing characteristics as they become activated. Naive T cells and B cells circulating in the bloodstream are not predetermined as to which compartment of the immune system they will end up in, and they enter Peyer’s patches and mesenteric lymph nodes through high endothelial venules (HEVs) (see Fig. 9.4). As in the systemic immune system, this process is controlled largely by the chemokines CCL21 and CCL19, which are released from the lymphoid tissues and bind the receptor CCR7 on naive lymphocytes. In the Peyer’s patches, this is assisted by binding of the mucosal vascular addressin MAdCAM-1 on HEVs to the L-selectin expressed on naive T cells. CXCR5 responding to CXCL13 produced in B-cell follicles is also important for recruitment of naive B cells to Peyer’s patches and isolated lymphoid follicles of the intestine. As in other secondary lymphoid tissues, if the naive lymphocytes do not see their antigen, they exit via the lymphatics and return to the bloodstream. If they encounter antigen in the GALT, the lymphocytes become activated and lose expression of CCR7 and L-selectin. This means that they have lost their ability to home to secondary lymphoid organs, because they cannot enter them via the HEVs (see Section 9-5).
Left panel: T and B lymphocytes primed by antigen in the Peyer’s patches or mesenteric lymph nodes arrive as effector lymphocytes in the bloodstream supplying the intestinal wall (see Fig. 12.8). The lymphocytes express the integrin α4:β7, which binds specifically to MAdCAM‑1 expressed selectively on the endothelium of blood vessels in mucosal tissues. This provides the adhesion signal needed for the emigration of cells into the lamina propria. Right panel: if primed in the small intestine, the effector lymphocytes also express the chemokine receptor CCR9, which allows them to respond to CCL25 (yellow circles) produced by epithelial cells of the small intestine; this enhances selective recruitment. Effector lymphocytes that have been primed in the large intestine do not express CCR9 but instead express CCR10. CCR10 may respond to CCL28 (blue circles) produced by colon epithelial cells to fulfill a similar function. Lymphocytes destined to enter the epithelial layer stop expressing the α4:β7 integrin and instead express the αE:β7 integrin. The receptor for this is E‑cadherin on the epithelial cells. These interactions may help keep lymphocytes in the epithelium once they have entered it.
Lymphocytes that have been activated in the mucosal lymphoid organs then travel to the mucosa, where they accumulate as effector cells. Although some T and B lymphocytes initially activated in Peyer’s patches may migrate directly into adjacent parts of the lamina propria, most leave via the lymphatics, pass through mesenteric lymph nodes, and eventually end up in the thoracic duct. From there they circulate in the bloodstream (see Fig. 12.8) and selectively reenter the intestinal lamina propria via small blood vessels. Antigen-specific naive B cells in the follicular areas of Peyer’s patches undergo isotype switching from IgM to IgA production there, but they only differentiate fully into IgAproducing plasma cells once they have returned to the lamina propria. As a result, plasma cells are rarely found in Peyer’s patches, and this is also true of effector T cells, which also only differentiate fully after arrival in the mucosa.