Indirect effects are independent of the way of tolerance induction.

Oral tolerance is a T-cell mediated phenomenon defined by a refractoriness to parenteral immunization with a protein that was first contacted by oral route. However, the authors have shown that the injection of a tolerated protein is not neutral for the immune system. In mice made tolerant to KLH by gavage, co-immunization with KLH and DNP-Ova blocks anti-DNP antibody formation. Anti-DNP antibody formation resulting from immunization with DNP-Ova can also be blocked by co-immunization with a dietary protein (zein) or a self component (fibrinogen). The inhibitory effects resulting from immunization with a tolerated protein, designated indirect effects, do not affect the induction of oral tolerance to another protein. These results support the hypothesis that active mechanism are involved in the maintenance of tolerance.