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

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.