Cellular kinetics of the intestinal immune response to cholera toxoid in rats.

Abstract

The aims of this study were (a) to find a regime of immunization with cholera toxoid in rats which would establish a high density of antitoxin containing cells (ACC) in the lamina propria of the intestine and (b) to determine the origin of the ACC. The best cellular response was achieved by a single i.p. dose of toxoid in FCA followed by an intraintestinal boost 2 wk later. ACC appeared in the thoracic duct lymph 2 days after boosting, reaching a peak of about 200,000 ACC/h at 3--4 days. This was followed by the appearance of large numbers of ACC in the intestine. The i.p. dose of toxoid by itself gave rise to very few ACC in the gut or thoracic duct lymph, but it had clearly primed the gut immune system for a secondary response. Priming was also achieved by the prolonged oral intake of toxoid. The importance of the intestinal route for boosting was shown by the failure of i.p. challenge to give an ACC response in the intestine after i.p. priming and the small response it provoked after oral priming. ACC among thoracic duct lymphocytes (TDL) and in the lamina propria contained predominantly IgA. Two observations indicated that the major source of the lamina propria ACC was from cells that emerged in the thoracic duct lymph after intraintestinal challenge. Firstly, the establishment of a thoracic duct fistula immediately before challenge prevented the appearance of ACC in the intestine. Secondly, many ACC appeared in the intestine of normal rats after the injection of TDL rich in ACC. Although homing of ACC precursors to the gut was not antigen-dependent, the distribution of ACC in the lamina propria was considerably influenced by the site of the intestinal challenge, the density of ACC being greatest at or distal to the site of injection of toxoid into the lumen of the gut.