Immunoglobulin E suppression and cytokine modulation in mice orally tolerized to beta-lactoglobulin.
This study was designed to confirm the tolerogenic properties of beta-lactoglobulin in a mouse model and to assess specific oral tolerance induction in humoral and cellular compartments. BALB/c mice were fed beta-lactoglobulin (BLG) or whey proteins at different ages and subsequently intraperitoneally challenged 5 days later with both BLG and a non-specific antigen, ovalbumin (OVA). Three weeks later, oral tolerance induction was analysed in CMP-fed, versus saline-fed mice, by measuring specific seric and intestinal antibody responses, delayed-type hypersensitivity (DTH), specific splenocyte proliferation, and cytokine secretion patterns. Three-week-old mice fed high doses of either whey proteins or BLG (respectively 3 mg/g or 5 mg/g of body weight) were found to achieve oral tolerization. At humoral and mucosal levels, anti-BLG immunoglobulin E (IgE) were suppressed in these groups when compared with saline fed mice. With respect to cellular responses, systemic DTH and lymphocyte proliferation to BLG were also inhibited in CMP-fed mice. Weaning time was determined to be the best period for oral tolerance induction. Kinetic analyses showed however, that a minimum of 2 weeks was required for oral tolerance detection. Finally, cytokine profiles indicated a reciprocal decrease of interleukin-2 (IL-2) and interferon-gamma (IFN-gamma) versus an increase of IL-10 and transforming growth factor-beta (TGF-beta) secretions in tolerized mice. Taken together, these results clearly showed that oral administration of high doses of cows' milk proteins can induce significant hyposensitization in mice, in a specific inhibition of T helper 1 (Th1) lymphocytes with the participation of suppressor cytokines.
Pecquet
S
S
Food Immunology, Nestec SA, Nestlé Research Centre Lausanne, Switzerland.
Pfeifer
A
A
Gauldie
S
S
Fritsché
R
R
D000367:Age Factors; D000485:Allergens / Q000008:administration & dosage* / Q000276:immunology; D000704:Analysis of Variance; D000818:Animals; D000917:Antibody Formation; D016207:Cytokines / Q000276:immunology*; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D007108:Immune Tolerance; D018928:Immunity, Mucosal; D007073:Immunoglobulin E / Q000276:immunology*; D007371:Interferon-gamma / Q000032:analysis; D016753:Interleukin-10 / Q000032:analysis; D007376:Interleukin-2 / Q000032:analysis; D007782:Lactoglobulins / Q000008:administration & dosage* / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D008894:Milk Proteins / Q000008:administration & dosage / Q000276:immunology; D018417:Th1 Cells / Q000276:immunology; D016212:Transforming Growth Factor beta / Q000032:analysis
D000485:Allergens; D016207:Cytokines; D007376:Interleukin-2; D007782:Lactoglobulins; D008894:Milk Proteins; D016212:Transforming Growth Factor beta; D016753:Interleukin-10; D007073:Immunoglobulin E; D007371:Interferon-gamma