In vivo kinetics of the immunoglobulin E response to allergen: bystander effect of coimmunization and relationship with anaphylaxis.
BACKGROUND
Murine models of hypersensitivity to allergens are useful tools for the evaluation of preclinical strategies to down-regulate the IgE response.


OBJECTIVE
To monitor the long-term kinetics of T and B cell responses to allergen as a function of allergen dosage and to investigate the effect of parallel immunization with a second antigen; to correlate B cell response with anaphylaxis.


METHODS
CBA/J mice were sensitized every other week by subcutaneous injections of phospholipase A2 (PLA2) and/or ovalbumin (OVA) adsorbed to alum. Specific antibody isotype responses, T cell proliferation, T cell cytokine production and anaphylaxis were assessed throughout the sensitization phase.


RESULTS
Low-dose immunization with PLA2 (0.1 microg) favoured a long-term, specific T helper (Th)2 response with high IgE and IL-4 production in contrast to high-dose PLA2 (10 microg) immunization, which biased the immune response towards a Th1 response with high IgG2a and low IL-4 production. Parallel immunization with an unrelated antigen (ovalbumin) had a significant bystander effect on the immunization with PLA2, which was also dose-dependent. Finally, although anaphylaxis as measured by rectal temperature drop was allergen-specific, it could be induced in the high- and low-dose immunization groups, and was not solely dependent on IgE levels.


CONCLUSIONS
Though low-dose allergen immunization appears to induce an efficient IgE response, the intensity and quality of this response may be modulated by bystander effects of parallel immunization and does not correlate strictly with anaphylaxis. This observation has relevance to the design of clinical immunotherapy protocols using murine model-based data.
Von Garnier
C
C
Division of Immunology and Allergy, Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland.
Astori
M
M
Kettner
A
A
Dufour
N
N
Corradin
G
G
Spertini
F
F
D000485:Allergens / Q000276:immunology* / Q000494:pharmacology*; D000707:Anaphylaxis / Q000276:immunology; D000818:Animals; D000918:Antibody Specificity / Q000187:drug effects / Q000276:immunology; D001402:B-Lymphocytes / Q000187:drug effects / Q000276:immunology; D024201:Bystander Effect / Q000187:drug effects / Q000276:immunology; D016207:Cytokines / Q000096:biosynthesis / Q000276:immunology; D004195:Disease Models, Animal; D004306:Dose-Response Relationship, Immunologic; D005260:Female; D005500:Follow-Up Studies; D000949:Histocompatibility Antigens Class II / Q000276:immunology; D007114:Immunization; D007073:Immunoglobulin E / Q000187:drug effects* / Q000276:immunology*; D007074:Immunoglobulin G / Q000187:drug effects / Q000276:immunology; D051379:Mice; D008808:Mice, Inbred CBA; D010047:Ovalbumin / Q000276:immunology / Q000493:pharmacokinetics; D010741:Phospholipases A / Q000276:immunology / Q000493:pharmacokinetics; D054467:Phospholipases A2; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology
D000485:Allergens; D016207:Cytokines; D000949:Histocompatibility Antigens Class II; D007074:Immunoglobulin G; D007073:Immunoglobulin E; D010047:Ovalbumin; D010741:Phospholipases A; D054467:Phospholipases A2