Suppression of Murine IgE Responses with Amino Acid Polymer/Allergen Conjugates

Abstract

Conjugates of poly-N-methylglycine (polysarcosine) and grass pollen allergen extracts, which have been previously shown to suppress murine IgE responses, were examined for their ability to modify lymphocyte activity in vitro. Allergen-specific T lymphocytes obtained from Balb/c mice gave a reduced response to syngeneic accessory cells pulsed with conjugates of polysarcosine-allergen compared with the response found using equivalent concentrations of native extract. Pretreatment of accessory cells with either polysarcosine or polysarcosine-allergen conjugates did not impair their subsequent ability to present grass pollen extract to immune T cells. Incubation of allergen-specific spleen cells with polysarcosine-allergen conjugates, but not with polysarcosine or allergen alone, resulted in specific cell-mediated suppression which significantly reduced proliferation in vitro. This activity was sensitive to treatment of cells with anti-T-lymphocyte antisera plus complement. Spleen cells obtained from animals immunised with allergen and taken 21 days after intravenous treatment with polysarcosine-allergen conjugates, a regimen that suppressed IgE antibody production, did not proliferate in the presence of grass pollen extract and failed to suppress a secondary lymphoproliferative response in vitro. Spleen cells obtained from similarly treated animals 3 days after the final polysarcosine-allergen injection responded to pollen extract in culture and, additionally, impaired a secondary response. The results suggest that the reduced IgE response found in animals treated with polysarcosine-allergen conjugates may be due, in part, to the generation of a short-lived antigen-specific T cell suppression.

Induction of Allergen-Specific T Cells by Conjugates of N-Formyl-Methionyl-Leucyl-Phenylalanine and Rye Grass Pollen Extract

“…Unlike F-MLP/rye conjugate, however, this material did not react with accessory cell-processed antigen cells but rather caused the in duction of suppressor cell subsets both in vivo and in vitro [4], As the induction of antigen-specific suppres sor cells may be an important requirement for the beneficial effects of allergen immunotherapy [14], the use of T' allergoid materials, such as F-MLP/rye which do not appear to alter significantly the cellular response to allergens, may be limited. One possibility, however, would be to use T' allergoids to expand the allergen-specific helper T cell pool of patients in a safe manner, and then to boost the antibody response with a small dose of unmodified allergen.…”

“…In particular, IgE suppression [4], modulation of inflammatory cell movement into sites of allergen challenge [12] and the late phase reaction to allergens [1] have all been identified as possible targets for altered T cell function.…”

Demonstration of Human, Rye Grass Pollen Extract-Specific, Helper and Suppressor Stimulating Activity of Modified Allergens by Effects on in vitro Hapten-Specific Antibody Production

“…Conjugates of polysarcosine and allergens have been shown to suppress murine IgE antibody by Tcell mechanisms [21]. In addition other modified allergens have been described that have extensively reduced IgE-reactivities and, poor IgG-inducing pro perties, but yet have various retained T-cell-stimulating capacities in experimental animals.…”

Polypeptoid polymers: Synthesis, characterization, and properties

“…[92] The reduced IgE response was transient [93] and was attributed partly to a short-lived antigen-specific T cell suppression. [94] It was further demonstrated that intranasal application of the conjugate can reduce the serum IgE antibody response that was brought about through exposure to the grass pollen extract, [95] providing a method to treat allergy. Kimura et al…”