Allergen-specific modulation of cytokine synthesis patterns and IgE responses in vivo with chemically modified allergen.
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.
Gieni
R S
RS
Department of Immunology, University of Manitoba, Winnipeg, Canada.
Yang
X
X
HayGlass
K T
KT
D000485:Allergens / Q000235:genetics / Q000276:immunology*; D000818:Animals; D001704:Biopolymers; D015704:CD4 Antigens / Q000502:physiology; D000939:Epitopes / Q000276:immunology*; D005786:Gene Expression Regulation; D005803:Genes, Immunoglobulin; D005976:Glutaral; D007073:Immunoglobulin E / Q000096:biosynthesis* / Q000235:genetics; D007074:Immunoglobulin G / Q000096:biosynthesis; D007371:Interferon-gamma / Q000096:biosynthesis* / Q000187:drug effects; D015847:Interleukin-4 / Q000096:biosynthesis*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008970:Molecular Weight; D010047:Ovalbumin / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley
D000485:Allergens; D001704:Biopolymers; D015704:CD4 Antigens; D000939:Epitopes; D007074:Immunoglobulin G; D015847:Interleukin-4; D007073:Immunoglobulin E; D007371:Interferon-gamma; D010047:Ovalbumin; D005976:Glutaral