Characterization of the mucosal immune response to 2-acetylaminofluorene-protein conjugates

Many environmental carcinogens gain access to the body only after traversing a mucosal surface. Due to their small size, most carcinogens are not recognized by the immune system and pass unhindered from the external to the internal environment. In previous studies, we demonstrated that secretory IgA directed against the carcinogen 2-acetylaminofluorene (AAF) can be elicited by covalently coupling AAF to the mucosal immunogen cholera toxin (CT). Rabbit intestines receiving secretions containing secretory IgA anti-AAF demonstrated a marked reduction in transmucosal absorption of carcinogen from the intestinal lumen to the mesenteric blood supply. In actively immune animals, however, recent data suggests that the disposition of luminal carcinogen may be influenced by the relative abundance of serum versus mucosally-based immunoglobulins. Our objective was to quantify the amount and isotype distribution of antibodies produced in response to AAF-carrier protein conjugates administered via different routes; using traditional parenteral carrier proteins and routes of administration, compared to mucosal carrier proteins and routes of administration. Administration of AAF-cholera toxin conjugates to isolated ileal (Thiry-Vella) loops in rabbits elicited a vigorous sIgA anti-AAF response in ileal secretions, with low levels of serum or intestinal IgG, or serum-based IgA produced concomitantly. All parenteral immunization protocols generated extremely high titers of serum IgG anti-AAF, with only moderate levels of sIgA produced concomitantly, even when mucosal boosting followed parenteral priming. When AAF-CT mucosal boosts were administered after intraperitoneal priming, a dramatic rise in serum, not secretory IgA was observed.