Anti-interferon gamma treatment blocks the ability of glutaraldehyde-polymerized allergens to inhibit specific IgE responses.

Abstract

SummaryThe lymphokines interleukin 4 and interferon y (IFN-y) have been shown to play an important role in regulation of polyclonal immunoglobulin E (IgE) and IgG2a responses in vitro and in vivo . We demonstrate here that treatment with chemically modified ovalbumin (OA) results in long-lived, 97-99% inhibition of allergen-specific murine IgE responses and 10 3 -10 4 -fold increases in anti-OA IgG2a. Responses to unrelated antigens are not affected. Treatment with unmodified OA under the same conditions fails to inhibit primary or secondary IgE responses or to increase IgG2a but does lead to pronounced increases in OA specific IgG1 production . Glutaraldehyde-polymerized ovalbumin (OA-POL)-induced changes in IgE and IgG2a responses are abrogated by in vivo treatment with purified monoclonal anti-IFN-y antibody (XMG 1 .2), a finding indicative of preferential IFN-y production upon exposure to chemically modified, but not native, allergen. The results suggest the possibility that the pattern of cytokine synthesis elicited after exposure to protein antigens, and the resulting immune response, may be dependent upon the form of antigen to which the individual is exposed and consequently may be subject to manipulation .

Hypoallergenic Variants of the <i>Parietaria judaica</i> Major Allergen Par j 1: A Member of the Non-Specific Lipid Transfer Protein Plant Family

“…For these reasons, Marsh et al [26]already introduced chemical polymerisation of the allergens to produce molecules with a reduced risk of inducing systemic reactions. Their safety has been tested in animals [27], showing the efficacy of this treatment, which has been attributed to the reduced IgE reactivity. Moreover, chemical modifications of crude extracts still represent problems in terms of the standardisation and purity of the extract.…”

Prevention of Allergen-Specific, Th2-Biased Immune Responses In Vivo: Role of Increased IL-12 and IL-18 Responsiveness

“…OVA-specific IgE titers were determined by passive cutaneous anaphylaxis while OVA-specific IgG1 and IgG2a/2c titers were determined by ELISA as described previously (24). Total IgE, IgG1, IgG2c (in B6 mice), and IgG2a (in BALB/c mice) were measured by ELISA using rat anti-mouse IgE or sheep anti-mouse IgG (for all IgG isotypes) (Southern Biotechnology Associates) as a capture Ab, followed by biotinylated rat anti-mouse IgE H chain mAb (Serotec), biotinylated goat anti-mouse IgG1 (Southern Biotechnology Associates), biotinylated goat anti-mouse IgG2c (Southern Biotechnology Associates), or biotinylated goat anti-mouse IgG2a (Southern Biotechnology Associates) and streptavidin-conjugated alkaline phosphatase.…”

Endogenous IL-12 synthesis is not required to prevent hyperexpression of type 2 cytokine and antibody responses

“…OVA-specific IgE was determined by 48 h passive cutaneous anaphylaxis, with IgG1 and IgG2a quantified by ELISA as previously described [50]. Total IgE was determined by ELISA using rat anti-mouse IgE (Southern Biotechnology Associates Inc., Birmingham, AL) followed by biotinylated 4 -specific rat antimouse IgE heavy chain mAb (Serotec, GB) and streptavidinalkaline phosphatase.…”