Not all parts of the mucosal immune system exploit the same tissue-specific chemokines, allowing localized compartmentalization of lymphocyte recirculation within the system. Thus, effector T and B cells primed in lymphoid organs draining the small intestine (mesenteric lymph nodes and Peyer’s patches) are most likely to return to the small intestine; similarly, those primed in the respiratory tract migrate most efficiently back to the respiratory mucosa. This homing is obviously useful in returning antigen-specific effector cells to the mucosal organ in which they will be most effective in fighting an infection or in controlling immune responses against foreign proteins and commensals. Nevertheless, some lymphocytes that have been primed in the GALT, for example, can also recirculate as effector cells to other mucosal tissues such as the respiratory tract, urogenital tract, and lactating breast. This overlap between mucosal recirculation routes gave rise to the idea of a common mucosal immune system, which is distinct from other parts of the immune system. Although this is now understood to be an oversimplification, it does have important implications for vaccine development, because it may enable immunization by one mucosal route to be used to protect against infection at another mucosal surface. An important example of this is the induction of IgA antibody production in the lactating breast by natural infection or vaccination of mucosal surfaces such as the intestine. This is because the vasculature of the lactating breast expresses MAdCAM-1 and the phenomenon is a crucial means of generating protective immunity that can be transmitted to infants by passive transfer of the antibodies in milk. A further example has been shown in experimental animals, in which nasal immunization has a special ability to prime immune responses in the urogenital tract against HIV. The mechanisms behind this are unknown.
12-7 Distinct populations of dendritic cells control mucosal immune responses.
As elsewhere, dendritic cells are important for initiating and shaping immune responses in mucosal tissues, and are located both in secondary mucosal lymphoid organs and scattered throughout the mucosal surfaces. Within Peyer’s patches, dendritic cells are found in two main areas. In the subepithelial dome region, dendritic cells can acquire antigen from M cells (Fig. 12.10). Both of the major subtypes of dendritic cells are present in the intestine (see Sections 6-5 and 9-1). In mice, the most abundant subset of dendritic cells in the Peyer’s patch expresses CD11b (αM integrin) and, when activated, tends to produce IL-23. This promotes development of TH17 cells and stimulates ILC3 cells, both of which produce IL-17 and IL-22 (see Sections 3-23 and 11-2). These dendritic cells express CCR6, the receptor for CCL20 produced by follicle-associated epithelial cells. In resting conditions, they reside beneath the epithelium and produce IL-10 in response to antigen uptake, maintaining a noninflammatory environment. However, during infection by a pathogen such as Salmonella, dendritic cells are rapidly recruited into the epithelial layer of the Peyer’s patch in response to the CCL20 that is released in increased quantities by epithelial cells in the presence of the bacteria. Bacterial products also activate the dendritic cells to express co-stimulatory molecules, allowing them to induce pathogen-specific naive T cells to differentiate into effector cells. Also in the T-cell area of Peyer’s patches are the less abundant CD11b-negative subset of dendritic cells, whose development requires the factor BATF3 and which produce the cytokine IL-12 (see Sections 6-5 and 9-9). CD11b-expressing dendritic cells are protective in many intestinal infections.