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This study demonstrates that the mucosal immune response to cholera toxin (CT) is compromised in old rats in comparison with young animals. The total number of immunoglobulin A (IgA)-secreting cells is similar or higher in the intestinal inductor and effector sites in old animals. However, the number of specifically induced anti-CT IgA antibody-secreting cells is lower in these tissues in comparison with those in young animals. The kinetics of this immune response in the different gut-associated lymphoid tissues studied suggests that the age-associated decline in the number of anti-CT IgA-secreting cells in the intestinal mucosa reflects impaired IgA immunoblast migration. Our data from lymphocyte adoptive transfer studies indicate that factors intrinsic to both the donor cells and the host recipient influence the migration of immunoblasts from the Peyer's patches to the effector site. For example, donor cells from old donors transferred to either young or old recipient rats migrate slower than young donor lymphocytes transferred into old host animals. In vitro studies clearly indicate that ageing does not impair antibody secretion by intestinal mucosal plasma cells. Therefore, the age-related decline in the intestinal mucosal immune response, e.g. diminished specific antibody titres in intestinal lavage, reflects fewer antibody-secreting cells in the mucosa.

Most research on the effects of ageing on gut mucosal immunity has been performed using rodents. However, there are inherent difficulties in the extrapolation of rodent data to humans. This study was initiated to define age-related changes in the gastrointestinal (GI) mucosal immune response in non-human primates. Antibody responses were measured in young and old rhesus monkeys (Macaca mulatta) immunized intraduodenally with cholera toxin (Ctx)/cholera toxoid (Ctd). Antigen-specific immunoglobulin A (IgA) antibody levels were markedly lower while anti-Ctx IgG and IgM titres were higher in the intestinal lavage samples of old as compared to young animals. Total IgA concentrations in gut lavage were independent of age or immune status. Measurable titres of anti-Ctx IgA in the saliva of both age groups support the common mucosal immune hypothesis. Flow cytometric analysis was used to identify age-related shifts in the expression of cell surface antigens on peripheral blood lymphocytes. The relative number of both IgA+ and Ctx+ cells was dramatically reduced in the blood of old monkeys. Collectively, these data suggest that the GI mucosal immune response to Ctx is compromised in old rhesus macaques. The deficit in immune responsiveness, namely reduced anti-Ctx IgA antibody secretion into the intestinal lumen, may be a consequence of alterations in the process of maturation and homing of specific antibody-secreting B lymphocytes.

Although ageing is accompanied by systemic immunodeficiencies, the status of the mucosal immune system in the elderly remains unresolved. The gastrointestinal mucosal immune response was evaluated in young, mature and old male rats subjected to intra-intestinal immunization with cholera toxin (CTx). Five days following secondary immunization, the alpha-CTx-IgA titre in the bile of immunized rats was markedly reduced, i.e. the values measured in young rats were approximately five-fold higher than those of old animals. alpha-CTx-IgA levels in non-immunized rats were negligible and age-related shifts in other antibody titres (alpha-CTx IgG and IgM) were not significant. The antibody response to CTx was not reflected in the total IgA content of the samples. The number of alpha-CTx antibody-containing cells (ACCs) in the small intestinal lamina propria was significantly reduced in old immunized rats in comparison with the young or mature animals. These data suggest that ageing compromises both non-immune cell (antibody transport by hepatocytes) and immune cell (number of ACCs in the gut wall) functions in response to cholera toxin immunization in this animal model.