ovalbumin and Helicobacter-Infections

The increase in the transcellular passage of intact antigens across the digestive epithelium infected with Helicobacter pylori may interfere with the regulation of mucosal immune responses. The aim of this work was to study the capacity of Helicobacter infection to inhibit the development of oral tolerance or to promote allergic sensitization and the capacity of a gastro-protective agent, rebamipide, to interfere with these processes in mice. Oral tolerance to ovalbumin (OVA) was studied in 48 C3H/He 4-week-old mice divided into four groups: (i) OVA-sensitized mice; (ii) OVA-"tolerized" mice (that is, mice that were rendered immunologically tolerant); (iii) H. felis-infected, OVA-tolerized mice; (iv) and H. felis-infected, OVA-tolerized, rebamipide-treated mice. Oral sensitization to hen egg lysozyme (HEL) was studied in 48 mice divided into four groups: (i) controls; (ii) HEL-sensitized mice; (iii) H. felis-infected, HEL-sensitized mice; and (iv) H. felis-infected, HEL-sensitized, rebamipide-treated mice. Specific anti-OVA or anti-HEL immunoglobulin E (IgE) and IgG1/IgG2a serum titers were measured by enzyme-linked immunosorbent assay. Additionally, the capacity of rebamipide to interfere with antigen presentation and T-cell activation in vitro, as well as absorption of rebamipide across the epithelial monolayer, was tested. H. felis infection led to the inhibition of oral tolerance to OVA, but rebamipide prevented this inhibitive effect of H. felis. H. felis infection did not enhance the sensitization to HEL, but rebamipide inhibited the development of this sensitization. Moreover, rebamipide inhibited in a dose-dependent manner antigen presentation and T-cell activation in vitro and was shown to be able to cross the epithelium at a concentration capable of inducing this inhibitory effect. We conclude that H. felis can inhibit the development of oral tolerance to OVA in mice and that this inhibition is prevented by rebamipide.

Topics: Administration, Oral; Alanine; Anaphylaxis; Animals; Antigen Presentation; Antigens; Chickens; Female; Gastritis; Helicobacter Infections; Immune Tolerance; Immunity, Mucosal; Immunoglobulin E; Immunoglobulin G; In Vitro Techniques; Intestines; Mice; Mice, Inbred C3H; Muramidase; Ovalbumin; Quinolones; T-Lymphocytes

Using IL-6-deficient (IL-6 -/-) or wild-type mice, we investigated whether IL-6 is involved in the intestinal adjuvant activity of cholera toxin (CT) and to what extent IL-6 is required for mucosal IgA responses against soluble protein Ags or live Helicobacter felis infection. In naive IL-6 -/- mice we found normal total IgA levels in serum, bronchial and intestinal lavage and unaltered frequencies of IgA plasma cells in intestinal lamina propria. In Peyer's patches (PP) and mesenteric lymph nodes (MLN) IgA-producing cells were as frequent in IL-6 -/- as in wild-type mice. Immunohistochemical analysis of PP revealed germinal centers that co-localized IgA+ cells, indicating B cell activation and isotype switching in situ in the intestinal immune inductive site. Phenotypic analysis of the distribution of conventional B-2 cells (B220+CD5-/Mac-1-) and B-1 cells (B220+, CD5+/Mac-1+) in intestine-associated tissues gave comparable results in IL-6 -/- and wild-type mice. The ability to respond with mucosal IgA following oral and intranasal immunization with specific Ag, KLH or OVA, in the presence of CT adjuvant or to live H. felis infection was similar in IL-6 -/- and wild-type mice. CT exerted strong and comparable adjuvant functions in IL-6 -/- and wild-type mice. Repeated oral immunizations with CT alone stimulated immune protection against CT-induced diarrhea in ligated loops that was of similar magnitude in IL-6 -/- and wild-type mice. We conclude that, although IL-6 has been ascribed a crucial role in terminal differentiation of IgA B cells in vitro, we found no evidence to support the notion that IL-6 is critically required for IgA B cell development or specific mucosal IgA responses in vivo.

Topics: Adjuvants, Immunologic; Animals; Antigens; B-Lymphocytes; Cholera Toxin; Female; Helicobacter; Helicobacter Infections; Hemocyanins; Immunity, Mucosal; Immunization; Immunoglobulin A, Secretory; Interleukin-6; Intestinal Mucosa; Male; Mice; Mice, Inbred C57BL; Mice, Knockout; Ovalbumin; Peyer's Patches