Enhanced triggering of mucosal immune responses by reducing splenic phagocytic functions

The role of the spleen in the rat mucosal immune response was investigated to three structural different pneumococcal polysaccharides, type 3, 4, and 14. Following immunization with pneumococcal polysaccharides, a larger amount of free antigen was found in several lymphoid tissues and an increased trapping of immune complexes was seen in follicles of splenectomized animals, as compared to control animals. Thus, clearance of the polysaccharides seems to be less effective after splenectomy. An increase in specific IgA antibody-containing cells (ACC) was found in mesenteric lymph nodes, villi and Peyer's patches in splenectomized rats. Apparently, splenectomy and subsequent decreased clearance of the antigen causes a prolonged stay of the antigen in the system and therefore specific ACC can be induced in different lymphoid tissues. After splenectomy the specific IgM and IgG antibody titers in serum decreased significantly for pneumococcal polysaccharides types 4 and 14, but not for type 3. Furthermore, the serum IgA antibody titers against the three types of polysaccharides under study were not affected. After elimination of macrophages in the spleen by treatment with dichloromethylene diphosphonate liposomes no ACC against type 14 were evoked in the marginal zone of the spleen, and again, an increase was observed in specific IgA ACC in mucosa-associated lymphoid tissues. The IgA antibody titers were also enhanced. In conclusion, IgA responses against pneumococcal polysaccharides can be elicited in absence of the spleen, i.e. at mucosal sites or in the draining lymph nodes. Furthermore, polysaccharide-specific IgA responses are enhanced after reduction of splenic phagocytic functions.