Gut-specific homing by antigen-stimulated T and B cells is determined in large part by the expression of the adhesion molecule α4:β7 integrin on the lymphocytes. This binds to the mucosal vascular addressin MAdCAM-1, found on the endothelial cells that line the blood vessels within the gut wall (see Fig. 12.9). Lymphocytes originally primed in the gut are also lured back as a result of tissue-specific expression of chemokines by the gut epithelium. In the case of the small intestine, CCL25 (TECK) produced constitutively by epithelial cells is a ligand for the receptor CCR9 expressed on gut-homing T cells and B cells. Within the intestine there seems to be regional specialization of chemokine expression, as CCL25 is not expressed outside the small intestine and CCR9 is not required for migration of lymphocytes to the colon. However, the colon, lactating mammary gland, and salivary glands express CCL28 (MEC, mucosal epithelial chemokine), which is a ligand for the receptor CCR10 on gut-primed lymphocytes and attracts IgA-producing B lymphoblasts to these tissues. The addressins and chemokine receptors involved in migration of activated lymphocytes to other mucosal surfaces are unknown.
Under most normal circumstances, only lymphocytes that first encounter antigen in a gut-associated secondary lymphoid organ are induced to express gut-specific homing receptors and integrins. As we shall see in the next sections, these molecules are induced or ‘imprinted’ on T lymphocytes by intestinal dendritic cells during antigen presentation. In contrast, dendritic cells from nonmucosal lymphoid tissues induce lymphocytes to express other adhesion molecules and chemokine receptors—for example, α4:β1 integrin (VLA-4), which binds VCAM-1; cutaneous lymphocyte antigen (CLA), which binds E-selectin; and the chemokine receptor CCR4—which direct them to tissues such as the skin (see Section 11-3). The tissue-specific consequences of lymphocyte priming in the GALT explain why effective vaccination against intestinal infections requires immunization by a mucosal route, because other routes, such as subcutaneous or intramuscular immunization, do not involve dendritic cells with the correct imprinting properties.
12-6 Priming of lymphocytes in one mucosal tissue may induce protective immunity at other mucosal surfaces.