Low-Dose Oral Tolerance due to Antigen in the Diet Suppresses Differentially the Cholera Toxin-Adjuvantized IgE, IgA and IgG Response

Abstract

Background: Cholera toxin (CT) is used as a mucosal adjuvant amongst other applications for studying food allergy because oral administration of antigen with CT induces an antigen-specific type 2 response, including IgE and IgA production. Priorly established oral tolerance due to antigen in the diet may radically impact on the CT-adjuvantized immune response. The present study served to evaluate the effect of priorly established low-dose oral tolerance on the CT-adjuvantized immune response towards a food antigen. Methods: Mice fed a diet containing microgram levels of the soy protein Kunitz soy-trypsin inhibitor (KSTI) (F0 mice) and mice fed a soy-free diet (F2 mice) were orally immunized with KSTI and CT. KSTI-specific serum IgG1, IgG2a, IgA and IgE and fecal IgA were monitored. KSTI-stimulated cell proliferation and interleukin (IL)-6 production were determined. Results: The anti-KSTI IgE and IgA responses in the F0 mice were substantially suppressed, while the IgG1 and IgG2a responses were not suppressed after five oral immunizations. The response suppression tended to decline with increasing numbers of immunizations suggesting that the suppression could be overcome by multiple immunizations. However, cell proliferation and IL-6 production were clearly suppressed even after five immunizations. Conclusions: Priorly established low-dose oral tolerance considerably suppressed the CT-adjuvantized KSTI-specific IgE, IgA and cellular immune response but only weakly and transiently the IgG response. The results revealed that low-dose oral tolerance includes the mucosal IgA response and that CT, albeit mediating an antigen-specific response, does not fully abrogate priorly established oral tolerance.

Effect of Maternal Dietary Cow’s Milk on the Immune Response to β-Lactoglobulin in the Offspring: A Four-Generation Study in Mice

“…This is in agreement with earlier studies in mice, which have reported oral tolerance induction towards proteins present in the diet [10, 11, 21, 22]. Whether this presence of oral tolerance in mice fed a BLG-containing diet is linked with the absence of hypersensitivity reactions remains to be tested.…”

“…Whether this presence of oral tolerance in mice fed a BLG-containing diet is linked with the absence of hypersensitivity reactions remains to be tested. However, in recent studies employing mice fed a soy-protein-containing diet, we found that the IgE response induced to soy protein by use of the Th2-driving mucosal adjuvant cholera toxin was considerably suppressed in the soy-protein-fed mice [22]. …”

Assessment of Lupin Allergenicity in the Cholera Toxin Model: Induction of IgE Response Depends on the Intrinsic Properties of the Conglutins and Matrix Effects

“…The mice used for immunization study 1 were bred and maintained on standard rodent diet containing soy protein, which has been shown to interfere with the immune response against soy proteins upon feeding with CT [26]. To investigate whether the distinct patterns of reactivity that were seen for Ig and IgE antibodies were affected by the diet, mice bred for 3 generations on a soy-free diet were orally immunized with lupin flakes and CT.…”

“…However, we did previously show that the IgG1 response against three different food proteins upon feeding in combination with CT depends on the protein concentration, whereas the IgE response exhibits a more individual response pattern [7]. As oral tolerance is more easily abrogated for IgG and IgA than for IgE [26], the differences in IgG and IgE responses towards the conglutins could be due to oral tolerance, possibly caused by crossreactivity with other legume proteins, as the mice employed in the first feeding study were fed a standard rodent diet containing soy proteins. Accordingly, we performed a new feeding experiment where mice bred on a soy-free diet were fed CT and lupin flakes.…”

“…In a previous study, we have shown that the feeding of CT alone to mice on soy-containing or soy-free feed did not give rise to a soy-specific antibody response [26]. …”