Brief Definitive Report INDUCTION OF A RAGWEED-SPECIFIC ALLERGIC STATE IN I r -GENE-RESTRICTED NONRESPONDER MICE*

A series of recent experiments from our laboratory have focused on the demonstration and characterization of a relatively IgE class-specific, nonantigen-specific, cellular suppressor mechanism involved in the murine IgE antibody response to allergens not controlled by H-2-1inked immune response (Ir) genes (1, 2). Such a suppressor T-cell mechanism was initially demonstrated indirectly by administering appropriate doses of ionizing X irradiation and cyclophosphamide at various stages in the IgE immune response (1). More direct evidence was derived from transfer experiments utilizing thymocytes or splenic theta-bearing cells to dampen the enhanced reaginic response induced by irradiation and cyclophosphamide (2). Furthermore, these suppressor cells exert their major effect by impeding T-helper cell induction although, as mentioned, sufficient numbers are capable of suppressing an ongoing IgE antibody response. It appears that the number and/or potencies of such cells varies among murine inbred strains without relatinship to H-2 haplotype since those animals which are "high" responders (e.g., BALB/c) of the IgE class to most allergens produce only moderately higher titers of specific reaginic antibody after elimination of this nonspecific suppressor mechanism, whereas "low" responders (e.g. AKR) or "nonresponders" (SJL) produce dramatically elevated titers of IgE antibody (1, 2); indeed, the latter mice produce levels which are equal to those of high responder mice which have not been manipulated. These latter observations demonstrated quite emphatically that under these experimental conditions "nonresponsiveness" of the IgE class (not related to responses to antigens controlled by Ir genes) is not the phenotypic expression of a genetic inability of certain strains to respond, but rather of their genetic capability to actively suppress reagin production. On the basis of these collective observations, experiments were designed to ascertain whether a similar suppressor mechanism might be operative in those situations in which nonresponsiveness of the IgE class is not polyclonal but