ORAL TOLERANCE INDUCTION WITH ALTERED FORMS OF OVALBUMIN

As a T cell-dependent phenomenon, oral tolerance is not expected to de pend necessarily on native configuration of antigens. We investigated the induction of oral tolerance with modified ovalbumin (Ova). Oral ad ministration of heat-denatured (HD-Ova) and cyanogen bromide-degraded ovalbumin was less effective than native Ova in inducing oral toleranc e in B6D2F1 mice. HD-Ova was effective in suppressing delayed-type hyp ersensitivity (DTH) reactions but did not suppress specific antibody f ormation. Injection of Ova directly into the stomach, but not into the ileum or cecum, suppressed subsequent immunization to DTH reactions. Gavage with protease inhibitors (aprotinin or ovomucoid) before gavage with Ova was ineffective in blocking tolerance induction. Treatment w ith hydroxyurea to destroy cycling cells 24 h before gavage with Ova b locked oral tolerance induction and also the possibility to passively transfer tolerance to naive recipients with the serum of mice gavaged with Ova 1 h before. The implications of these findings about oral tol erance induction are discussed.