Allergen-specific modulation of cytokine synthesis patterns and IgE responses in vivo with chemically modified allergen.

Abstract

Hypersensitivity and IgE synthesis are highly dependent on the balance in which production of IL-4 and IFN-gamma is induced. An immunologic approach that alters the dominant pattern of cytokine synthesis and antibody production that is elicited after exposure to native allergen is described. High M(r), glutaraldehyde-polymerized OVA administered (i.p.) before or after immunization with unmodified OVA induces > or = 95% inhibition of specific IgE synthesis concomitant with 300- to 800-fold increases in IgG2a production in C57BL/6 mice. These changes result from a genetically controlled shift in the pattern of cytokine production within the allergen-specific T cell repertoire as demonstrated by i) susceptibility of the changes induced upon administration of modified allergen to in vivo treatment with anti-IFN-gamma mAb and ii) a 5- to 7-fold increase in the ratio of IFN-gamma:IL-4 synthesis after overnight culture directly ex vivo. This system should prove useful in identification of the factors which are influential in the commitment of T cells to Th1- or Th2-like patterns of cytokine synthesis. Moreover, as defective induction of IFN-gamma by allergen-specific T cells appears to play a role in elevated IgE synthesis and human allergy, this approach may have therapeutic potential.