THE INDUCTION OF TOLERANCE TO ALLERGENIC CHEMICALS *

The first recognition of tolerance and partial tolerance to attempted sensitization with simple allergenic chemicals is described. A proper designation would be the Frei-Sulzbeger-Chase phenomenon. Coupling with self occurs in these experiments; there is not only resistance to developing contactant-type sensitivity but also to synthesis of immunoglobulins toward hapten-self complexes. The onset of tolerance is initiated by small doses of haptens. Various facets of these investigations speak strongly against a concept of clonal deletion as an explanation. The concept of the relative numbers of suppressor and effector cells also argues against clonal deletion. Evidence exists that tolerance can be transferred to syngeneic animals by cells during parabiosis (Polak, this volume). Contact sensitivity can be imposed on a tolerized guinea pig through a transfer of cells from outbred sensitized donors, but the tolerance remains after the transferred cells have been rejected. Tolerance could not be overcome in inbred guinea pigs by infusing normal or functionally "labeled" cell populations from close relatives before attempting sensitization, a fact that supports the existence of overwhelmingly large numbers of suppressor cells. Various routes of application have been explored to find a way to establish the tolerant state. The most successful are (1) feeding of small doses and (2) two intravenous injections of massive doses of DNP- or TNP-benzene sulfonates. Several other methods will effect tolerance in about half the animals, but experimental sensitization is the only method that will locate the tolerized animals.