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

J Immunol. 1993 Jan 1;150(1):302-10.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Allergens / genetics
  • Allergens / immunology*
  • Animals
  • Biopolymers
  • CD4 Antigens / physiology
  • Epitopes / immunology*
  • Gene Expression Regulation
  • Genes, Immunoglobulin
  • Glutaral
  • Immunoglobulin E / biosynthesis*
  • Immunoglobulin E / genetics
  • Immunoglobulin G / biosynthesis
  • Interferon-gamma / biosynthesis*
  • Interferon-gamma / drug effects
  • Interleukin-4 / biosynthesis*
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred C57BL
  • Molecular Weight
  • Ovalbumin / pharmacology
  • Rats
  • Rats, Sprague-Dawley

Substances

  • Allergens
  • Biopolymers
  • CD4 Antigens
  • Epitopes
  • Immunoglobulin G
  • Interleukin-4
  • Immunoglobulin E
  • Interferon-gamma
  • Ovalbumin
  • Glutaral