Monomeric Allergoid Intragastric Administration Induces Local and Systemic Tolerogenic Response Involving IL-10-Producing CD4⁺CD25⁺T Regulatory Cells in Mice

Abstract

The efficacy of sublingual immunotherapy, at present one of the treatments of choice for respiratory allergy, relies on the tolerance induced by oral mucosa-associated immune system; however, the gut-associated lymphoid tissue (GALT: Peyer's patches and isolated lymphoid follicles) and mesenteric lymph nodes could also be involved, being stimulated by the ingested part of the allergen extract. The aim of the present study is to assess whether the exposure of the allergen exclusively to the GALT induces a tolerogenic response. To this purpose, mice were sensitized with ovalbumin or Par j 1 allergens. The corresponding gastric-resistant monomeric allergoids were then administered via orogastric gavage. After treatment, all mice were tested for: serum IgE, in vitro Th1 and Th2 cytokine release by allergen-stimulated peripheral blood lymphocytes, CD4+CD25+ and CD4+CD25+IL-10+ T cells in Peyer's patches, mesenteric lymph nodes and spleen. Compared to the control, sensitized groups showed higher levels of serum IgE, lower frequency of CD4+CD25+IL-10+ T cells, at all sites, and higher amounts of in vitro-released IL-4, IL-6 and TNF-α. Compared to the sensitized groups, higher frequency of CD4+CD25+IL-10+ T cells was observed in the spleen of both Par-j 1 and OVA sensitized/treated groups and, only for ovalbumin-treated mice, in the Peyer's patches and mesenteric lymph nodes, IgE and in vitro cytokines were significantly lower and equivalent to the control group. The results give the first evidence that the intragastric-restricted administration of gastric-resistant allergens restores local and peripheral tolerance in allergen-sensitized mice.

Dose-Dependent Clinical and Immunological Efficacy of Sublingual Immunotherapy with Mite Monomeric Allergoid

“…These results are due to its specific characteristics that differentiates it from the other molecules used for specific immunotherapy. It is optimally absorbed through the oral mucosa, being of low molecular weight (6), moreover, the carbamylation process increases its resistance to enzymatic degradation at the gastrointestinal tract, thus improving its bioavailability (6)(7)(8). Furthermore, it reduces IgEbinding capacity with a consequent low risk for side effects as shown by our and all other studies in literature (1-5, 9, 18,20).…”

Synergy of Transforming Growth Factor Beta 1 and All Trans Retinoic Acid in the Treatment of Inflammatory Bowel Disease: Role of Regulatory T cells

“…We have already alluded to the potential of RA/TGFβ based Treg conversion as a strategy aimed at T1DM [100, 101]. However, a number of reports suggest the potential for an even more general expansion to other indications including rheumatoid arthritis [127], multiple sclerosis [128] and allergic disease [129]. …”

Induction of Potent and Long-Lived Antibody and Cellular Immune Responses in the Genitorectal Mucosa Could be the Critical Determinant of HIV Vaccine Efficacy

“…Some of these characteristics have been traditionally attributed to mucosal immunization including intranasal, intravaginal, intrarectal, and oral or sublingual delivery routes (230, 234, 235). Possibly, delivery of a vaccine at one mucosal site may induce immunity at peripheral mucosal sites via the common mucosal immune system (236, 237), although this hypothesis is disputed by studies showing compartmentalization of the mucosal immune network (238). …”