Exposure of mice to aerosolized ovalbumin (OA) once weekly for 5 min, or once weekly to 10 microgram OA in PBS intranasally, elicited transient IgE responses which declined by the seventh week. When these animals were challenged intraperitoneally (i.p.) with soluble or alum-precipitated OA, their subsequent IgE responses were markedly suppressed relative to controls. In contrast, i.p. challenge provoked hemaagglutinating antibody (HA) responses to OA in the same animals which were considerably more vigorous than in controls. Adoptive transfer experiments employing splenocytes from mice repeatedly exposed to OA via the respiratory tract revealed the presence of suppressor cells active against OA-specific IgE but not HA responses. Radiotracer studies employing 125I-OA, administered intranasally and by aerosol, indicated that much of the antigen rapidly became associated with the gut.

Immunization of a number of inbred mouse strains intraperitoneally with low levels (1-100 micrograms) of ovalbumin (OA) or ovomucoid (OM) in the absence of adjuvant, revealed marked strain differences in IgE responsiveness. High-OA-responder strains such as Balb/c exhibited PCA titre up to 256 in the primary response, and up to 1,280 in the secondary, while non-responders such as SJL and NZB remained PCA negative; similar variations were found in the response of the strains to OM. Repeated immunization of high-OA-responder mice with low doses of antigen without adjuvant elicited anamnestic second and tertiary HA antibody responses. In contrast, IgE responses exhibited anamnestic secondary responses, but were not further boosted by tertiary stimulation. Instead, a 'persistent' high IgE response of the type previously associated with the use of specialized adjuvants, developed in these mice. Fractionation of the OA antigen by gel filtration yielded molecular species (dimers pentamers) of considerably greater IgE-immunogenicity than either monomeric OA or very highly aggregated forms. Immunization of high-OA-responder mice with the former permitted lowering of the threshold for induction of adjuvant-independent primary OA-IgE responses to a single 1.0 microgram dose, and the threshold for priming to 0.1 microgram.

The addition of syngeneic alveolar macrophages (AM) to mitogen-stimulated lymphocyte cultures from the rat and the guinea-pig resulted in markedly dissimilar effects upon in vitro blastogenesis, guinea-pig AM stimulating the response and rat AM exhibiting strong suppressive activity. The capacity of guinea-pig and rat AM to initiate antigen-specific blastogenesis was also examined. Ovalbumin-immune lymph node cells from guinea-pigs were passed through nylon wool columns to deplete macrophages. This process abolished their capacity to respond to the antigen via blastogenesis. The addition of ovalbumin-pulsed AM to these cultures restored their blastogenic responsiveness, and did so with considerably greater efficiency than was observed employing peritoneal macrophages from the same animals. Identical manoeuvres in the rat again yielded opposite results; the addition of rat AM to syngeneic antigen-stimulated lymphoid cell cultures consistently suppressed blastogenesis, an effect not seen employing peritoneal macrophages from the same species.

The ability of macrophage-associated antigen to both prime for, and subsequently trigger, IgE responses in inbred rats and mice was investigated. Peritoneal exudate cells briefly pulsed in vitro with ovalbumin (PEC-OVA) served as the immunogen, and both primed and unprimed animals as recipients. The experiments revealed that the intraperitoneal administration of relatively small numbers of PEC-OVA, while generally ineffective in inducing primary IgE responses in immunologically virgin mice, successfully primed the latter for secondary IgE responses following later challenge. Furthermore, PEC-OVA was highly effective in triggering vigorous secondary IgE responses in primed mice, producing PCA titres up to 10,000 in both moderate and high IgE-responder strains. The data further indicate that the IgE response induced in mice by PEC-OVA is transient, it exhibits a markedly lower threshold (in both the primary and secondary response) than corresponding haemagglutinating antibody responses, and is MHC-restricted. In the rat strain employed (low IgE-responder WAG), PEC-OVA administration evoked vigorous haemagglutinating antibody responses in pre-immunized rats, and primed immunologically virgin animals for similar secondary responses. However, PEC-OVA was only weakly immunogenic/antigenic for IgE responses in WAG rats.