Different expression of IL-2 receptor alpha-chain on a lamina propria T cell population and goblet cells in rats orally tolerized or sensitized to ovalbumin (OA) after colonization with an OA-producing Escherichia coli.
The aim of this study was to compare the local gut immune response in sensitized and orally tolerized experimental animals. The development of IgE/IgG antibodies and the DTH to OA was studied in rats made orally tolerant to OA and compared with sensitized control rats after colonization with an Escherichia coli genetically engineered to produce OA. At 3 weeks of age, pups were weaned onto a standard diet without OA or an OA-containing diet for 4 weeks and then switched to a standard diet without OA. Both groups of rats were parenterally immunized with a mixture of OA and human serum albumin (HSA) in Freund's complete adjuvant when they were 8 weeks old. After DTH measurement 2 weeks later, all rats were colonized with an E. coli producing OA for 5 days. The local immune response in the small intestine was assessed, using immunohistochemistry, as the expression of MHC class II molecules and IL-2 receptor (IL-2R) alpha-chain. The OA-tolerant rats showed the classical signs of oral tolerance, with a reduced IgE and IgG antibody and DTH response to OA before colonization. The difference between the two groups in the anti-OA antibody response became even more pronounced after colonization with the E. coli that produce OA. Rats orally tolerant to OA maintained a normal villus architecture after colonization, with a normal expression of MHC class II molecules similar to non-treated adult rats, but with a significantly higher (P = 0.004) expression of IL-2R alpha-chain on T cells in the lamina propria of the villus core compared with sensitized control rats. The tolerant rats showed a very weak staining with the anti-IL-2R alpha-chain-specific antibody on a few goblet cells in only one out of seven rats. In the sensitized control rats, a marked local immune response was seen with an intense staining with a monoclonal anti-IL-2R alpha-chain-specific antibody on goblet cells in five out of seven rats (P = 0.019) and also an increased expression of MHC class II molecules in the epithelial cells and cells in the lamina propria of all rats. Rats orally tolerant to OA maintained a normal villus architecture after colonization, but with a significantly higher (P = 0.004) expression of IL-2R alpha-chain on T cells in the lamina propria of the villus core compared with sensitized control rats. The novel finding that goblet cells express IL-2R alpha-chain and the striking difference in expression of the receptor and the numbers of goblet cells between tolerant and sensitized rats may suggest a direct T cell regulation of the goblet cells. A possibility that oral tolerance might be maintained by the activated T cells expressing IL-2R alpha-chain in the lamina propria of the villus core is also discussed.
Dahlman-Höglund
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A
Department of Clinical Immunology, University of Göteborg, Sweden.
Ahlstedt
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S
Hanson
L A
LA
Dahlgren
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U
Telemo
E
E
D000284:Administration, Oral; D000818:Animals; D001431:Bacteriological Techniques; D001485:Basement Membrane / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D004926:Escherichia coli / Q000378:metabolism; D004927:Escherichia coli Infections / Q000378:metabolism; D005260:Female; D005822:Genetic Vectors / Q000378:metabolism; D007108:Immune Tolerance / Q000276:immunology*; D007114:Immunization / Q000379:methods*; D007413:Intestinal Mucosa / Q000166:cytology / Q000276:immunology* / Q000378:metabolism*; D010047:Ovalbumin / Q000008:administration & dosage / Q000096:biosynthesis* / Q000276:immunology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D015375:Receptors, Interleukin-2 / Q000096:biosynthesis*; D013601:T-Lymphocytes / Q000378:metabolism*
D015375:Receptors, Interleukin-2; D010047:Ovalbumin