The engagement of oral‐associated lymphoid tissues during oral versus gastric antigen administration

Summary The role of oral‐associated lymphoid tissues during induction of oral tolerance still remains elusive. Therefore, the aim was to compare T‐cell activation and induction of tolerance to ovalbumin (OVA) presented through either of two routes; deposited into the oral cavity, or the stomach, thereby bypassing the oral cavity. OVA was administered by the oral or gastric route to BALB/c mice that had received OVA‐specific DO11.10+ CD4+ T cells, stained with CellTrace™ Violet dye, through intravenous injection. Proliferating OVA‐specific T cells were detected in the nose‐associated lymphoid tissues (NALT) and the cervical, mesenteric and peripheral lymph nodes at different time‐points following OVA exposure. OVA‐specific T‐cell proliferation was initially observed in the NALT 1 hr after oral, but not gastric, administration. However, at day 1, proliferation at this site was also detected after gastric administration and profound proliferation was observed at all sites by day 4. For the oral route the degree of proliferation observed was lower in the peripheral lymph nodes by day 4 compared with the other sites. These results demonstrate a similar activation pattern achieved by the two routes. However, the NALT distinguishes itself as a site of rapid T‐cell activation towards fed antigens irrespective of feeding regimen. To evaluate induction of tolerance a semi‐effective OVA dose was used, to detect differences in the degree of tolerance achieved. This was performed in a model of OVA‐induced airway hypersensitivity. No differences in tolerance induction were observed between the two administration routes. The role of oral‐associated lymphoid tissues during induction of oral tolerance still remains elusive. We demonstrate, for the first time, that oral‐associated lymphoid tissues, especially the nose‐associated lymphoid tissues, seems to be of importance for T‐cell activation upon exposure to an antigen as this is one of the first sites that exhibits T‐cell activation irrespective of administration route. Further, the degree of tolerance achieved by oral or gastric administration of the antigen was equal, which implies that the oral‐associated lymphoid tissues do not contribute in any additional way to the induction of oral tolerance.