Unique Characteristics of the Intestinal Immune System as an Inductive Site after Antigen Reencounter

Abstract

Background Immunization prepares the body for a reencounter with the microbe. Information on the targeting of immune effector cells during secondary immune response—that is, lymphocyte homing—is scarce. In the present study, the homing potentials of lymphocytes are examined after antigen reencounter at mucosal versus nonmucosal sites. Methods Orally or parenterally immunized volunteers were reimmunized orally or parenterally with Salmonella typhi Ty21a, and the expression of the gut homing receptor (HR), α₄β₇, and of the peripheral lymph node HR, L-selectin, was investigated in circulating antigen-specific antibody-secreting cells (ASCs). Lymphocytes were sorted by HR expression and examined for antibody production, by use of an enzyme-linked immunospot assay. Results After oral reimmunization, 90% of ASCs were α₄β₇ positive and 88% were L-selectin positive, an expression profile that differed significantly from that found after oral primary immunization. After parenteral reimmunization, 45% of ASCs were α₄β₇ positive and 79% were L-selectin positive, similar to the results after parenteral primary immunization. The route of priming had no effect on HR patterns in either case. Conclusions Homing potentials of lymphocytes depend on the site of antigen reencounter. Whereas the HR profile after parenteral reimmunization resembles that after primary immunization, the profile after oral reimmunization is uniquely characterized by high expression of both HRs, suggesting gut-localized memory and effective homing ability to both the mucosal and systemic immune system. These data may prove valuable in the search for the most effective immunization route in humans.