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Zearalenone (ZEN) is one of the most active natural estrogenic compounds that induces apoptosis. This study has been prompted by the widespread occurrence of ZEN in food and feed and limited knowledge about the effects of exposure to low doses of ZEN on the immune system. The aim of the study was to verify the hypothesis that low doses of ZEN contribute to induction of apoptosis and inhibition of proliferation in lymphocytes of the germinal centers (GC) of ileal Peyer's patches (IPP) in pigs. The experiment was performed on 30 female Polish Large White pigs, aged 2 months, with body weight of 15-18 kg, divided into two groups: control (C, n=15) and experimental (Z, n=15). On days 14, 28 and 42 of exposure to ZEN (100 μg kg−1 feed day−1), apoptosis in IPP GC was evaluated histologically in HE-stained specimens, immunohistochemically by active caspase-3 staining and in mononucleosome and oligonucleosome detection-based ELISA. Proliferation was evaluated histologically by mitosis detection in HE-stained specimens, immunohistochemically by PCNA staining and in the MTT tetrazolium salt colorimetric assay detecting mitogenic responses of B cells to LPS. Exposure to low doses of ZEN for several weeks intensified apoptosis and weakened proliferation in IPP lymphocytes. ZEN influences gut-associated lymphoid tissue (GALT) by decreasing the expression of CD21+ on B cells and by increasing the percentage of B1 cell populations.

The ileal Peyers patches (IPP) of newborn germfree (GF) piglets were isolated into blind loops and the piglets colonized with a defined probiotic microflora. After 5 weeks, IgA levels in the intestinal lavage (IL) of loop piglets remained at GF levels and IgM comprised ∼70% while in controls, IgA levels were elevated 5-fold and comprised ∼70% of total Igs. Loop piglets also had reduced serum IgA levels suggesting the source of serum IgA had been interrupted. The isotype profile for loop contents was intermediate between that in the IL of GF and probiotic controls. Surprisingly, colonization alone did not result in repertoire diversification in the IPP. Rather, colonization promoted pronounced proliferation of fully switched IgA(+)IgM(-) B cells in the IPP that supply early, non-diversified "natural" SIgA antibodies to the gut lumen and a primary IgA response in serum.

Helicobacter heilmannii induces gastric lymphoid follicles in mice. However, the pathogenic mechanisms behind the induction of gastric lymphoid follicles by H. heilmannii infection have not been elucidated. The aim of this study was to investigate the roles of Peyer's patches (PP) in H. heilmannii-induced immune responses and the development of gastric lymphoid follicles. C57BL/6J and PP deficient mice were infected with H. heilmannii, and in addition to histological and immunohistological examinations, the expression levels of cytokines and chemokines in gastric mucosa were investigated. Gastric lymphoid follicle formation and the infiltration of dendritic cells, B cells, and helper T cells were milder in the PP-deficient mice 1 month after infection, but they were similar in both types of mice after 3 months. The mRNA expression levels of tumor necrosis factor α and CC chemokine ligand 2 were significantly high in the H. heilmannii-infected groups, and CXC chemokine ligand 13 expression was significantly increased in the infected C57BL/6J wild-type mice 1 month after infection. These results suggest that PP are not essential for the formation and development of gastric lymphoid follicles induced by H. heilmannii infection, although they are involved in the speed of gastric lymphoid follicle formation.

The role of lactic acid bacteria in gut mucosal immunity was investigated by comparing the enhanced effects in the Peyer's patches and spleen of BALB/c mice fed daily with Lactobacillus paracasei subsp. paracasei NTU 101 for 3 to 9 weeks. After feeding with Lactobacillus, the percentage of CD4+ T cells in both Peyer's patches and the spleen was significantly increased; however, expression of CD 154 molecules, which play a pivotal role in cell-to-cell communication, on CD4+ T cells and the percentage of B220+ B cells increased only in Peyer's patches. Compared with systemic serum IgA, Peyer's patch-derived immunomodulation induced higher levels of intestinal IgA+-producing cells in the lamina propria. Our data also showed that feeding with Lactobacillus induced stronger CD4+ T cell-dendritic cell interaction, enhanced CD4+ T cell and B cell proliferation, and increased IL-1beta, IL-10, IL-12, IFN-gamma, and TNF-alpha mRNA expression in Peyer's patches, but not in the spleen. Here, we demonstrate that following Lactobacillus treatment, Peyer's patches exhibited a more distinct capacity to induce CD4+ T cell-dendritic cell interactions, lymphocyte proliferation, and cytokine secretion than the spleen, and thereby promoted greater intestinal IgA production that could enhance immunosurveillance to prevent intestinal infections or other intestinal pathologies.

The purpose of this study was to evaluate the possibility of lectin-coupled microspheres to improve the targeted delivery of protein antigens to the lymphoid tissues of mucosal surfaces. Bovine serum albumin containing acid phosphatase model protein and polystyrene microspheres were coupled with mouse M-cell-specific Ulex europaeus lectin. The coupling efficiency, physical characteristics and the binding capabilities of the microspheres to the follicle associated epithelium of the Peyer's patches were evaluated in vitro and ex vivo in mice intestine. The results showed that coupling of lectin to albumin microspheres did not significantly affect the bioactivity of the encapsulated acid phosphatase model protein. It was also shown that there was preferential binding of the lectin-coupled microspheres to the follicle-associated epithelium. It was concluded from the results of the study that coupling of ligands such as lectin specific to cells of the follicle associated epithelium can increase the targeting of encapsulated candidate antigens for delivery to the Peyer's patches of the intestine for improved oral delivery.

Most of the immunoglobulin A (IgA) in the gut is generated by B cells in the germinal centers of Peyer's patches through a process that requires the presence of CD4 + follicular B helper T(T FH ) cells. The nature of these T FH cells in Peyer's patches has been elusive. Here, we demonstrate that suppressive Foxp3 + CD4 + T cells can differentiate into T FH cells in mouse Peyer's patches. The conversion of Foxp3 + T cells into T FH cells requires the loss of Foxp3 expression and subsequent interaction with B cells. Thus, environmental cues present in gut Peyer's patches promote the selective differentiation of distinct helper T cell subsets, such as T FH cells.

Normal organogenesis requires co-ordinate development and interaction of multiple cell types, and is seemingly governed by tissue specific factors. Lymphoid organogenesis during embryonic life is dependent on molecules the temporal expression of which is tightly regulated. During this process, haematopoietic 'inducer' cells interact with stromal 'organizer' cells, giving rise to the lymphoid organ primordia. Here we show that the haematopoietic cells in the gut exhibit a random pattern of motility before aggregation into the primordia of Peyer's patches, a major component of the gut-associated lymphoid tissue. We further show that a CD45+CD4-CD3-Il7Ralpha-c-Kit+CD11c+ haematopoietic population expressing lymphotoxin has an important role in the formation of Peyer's patches. A subset of these cells expresses the receptor tyrosine kinase RET, which is essential for mammalian enteric nervous system formation. We demonstrate that RET signalling is also crucial for Peyer's patch formation. Functional genetic analysis revealed that Gfra3-deficiency results in impairment of Peyer's patch development, suggesting that the signalling axis RET/GFRalpha3/ARTN is involved in this process. To support this hypothesis, we show that the RET ligand ARTN is a strong attractant of gut haematopoietic cells, inducing the formation of ectopic Peyer's patch-like structures. Our work strongly suggests that the RET signalling pathway, by regulating the development of both the nervous and lymphoid system in the gut, has a key role in the molecular mechanisms that orchestrate intestine organogenesis.

Other factors than the allergen itself may be of importance in the development of food allergy. This report describes the influence of the immunosuppressive compound bis(tributyltin)oxide (TBTO), present in the food chain, on the development of food allergy to peanut or ovalbumin in Brown Norway (BN) rats. To study these effects BN rats were sensitized to either 1 or 10 mg peanut or ovalbumin by daily oral gavage and the TBTO-groups were fed a diet containing 80 mg TBTO per kg diet. Co-exposure to TBTO not only resulted in decreased general immunologic parameters such as weights of mesenteric lymph nodes and Peyer's patches, lymphocyte proliferation rates in splenocytes, but also on allergic parameters. In the peanut allergen-model TBTO decreased allergen-specific Th2 cytokine production by spleen cells, number of eosinophilic and basophilic granulocytes in the blood and production of mast cell protease II after oral food challenge. In the ovalbumin allergen-model TBTO decreased the number of eosinophilic and basophilic granulocytes, allergen-specific IgE and production of mast cell protease II after oral food challenge. The data imply that in the process of risk assessment of food allergy attention should be given to immunomodulating compounds present in the diet. © 2007 Elsevier Ireland Ltd. All rights reserved.

Peyer's patches constitute both an inductive immune site and an enteropathogen invasion route. Peyer's patch mucosae from porcine jejunum were mounted in Ussing chambers, and either Salmonella choleraesuis vaccine strain SC-54 or non-pathogenic rodent and porcine Escherichia coli strains contacted the Peyer's patch mucosa for 90 min. Internalized bacteria were quantified by a gentamicin resistance assay. Monodansylcadaverine (300 microM, luminal addition), an inhibitor of clathrin-mediated endocytosis, significantly inhibited internalization of both E. coli strains relative to tissues untreated with the inhibitor; internalization of SC-54 was unaffected. The actin-disrupting agent cytochalasin D (10 microM, luminal addition), inhibited internalization of pig-adapted E. coli but not that of rodent-adapted E. coli or SC-54. Internalization of SC-54 and non-pathogenic E. coli in Peyer's patches appears to occur through different cellular routes.

Background and aims: Surgical management of extrahepatic cholestasis is frequently complicated by bacterial translocation and severe liver injury. The aim of this study was to clarify the involvement of Toll-like receptors (TLRs) in the pathogenesis of bacterial translocation and liver injury in obstructive cholestasis. Methods: TLR2 deficient (TLR2 −/− ), MyD88 −/− , Jα281 −/− , gld / gld , and lpr / lpr mice, all of which have a C57BL/6 background, and C3H/HeN and TLR4 mutated C3H/HeJ mice were subjected to bile duct ligation (BDL). Faecal IgA and serum alanine aminotransferase levels were determined after BDL. Apoptosis was examined by histological and flow cytometric analyses of cells from Peyer’s patches and the liver. Results: The size and number of B cells in Peyer’s patches markedly decreased on day 3 after BDL. Increased apoptosis in Peyer’s patch B cells was evident on day 1 after BDL in control mice but not in lpr / lpr , MyD88 −/− , or C3H/HeJ mice. On the other hand, TLR2 and Fas ligand expression on intrahepatic NK1.1 + T cells increased on day 1 after BDL in C57BL/6 mice. Liver injury and apoptosis were evident on day 1 after BDL in control and C3H/HeJ mice but were significantly reduced in TLR2 −/− , Jα281 −/− , gld / gld , and lpr / lpr mice. Conclusions: TLR4 and TLR2 may play important roles in Fas dependent apoptosis in Peyer’s patch B cells and hepatocytes, respectively, at an early stage after BDL in mice.

Summary Child mortality in diarrhoeal disease is increased significantly by vitamin A deficiency in poor countries. The pathological mechanisms are not known in detail. However, in this paper we report that vitamin A-deficient Wistar rats had much reduced IgA+ plasma cells in the ileal lamina propria (eightfold reduction from 470 cells/mm2, P = 0·009), as well as a prominent reduction of CD4+ cells in the parafollicular regions of ileal Peyer's patches (reduction from 7200 to 105 cells/mm2, P = 0·009). IL-2Ralpha-chain (CD25) positive lymphocytes in the ileal Peyer's patches were also reduced significantly in vitamin A deficiency (from 1400 to 300 cells/mm2, P = 0·009). The density of CD8 cells tended to be increased relative to the control animals (from 5100 to 6000 cells/mm2, not statistically significant). In conclusion, the marked decrease of lamina propria IgA+ plasma cells may be one cause of the high diarrhoeal mortality in vitamin A deficiency. This, in turn, appears to be related to reduced numbers of activated or regulatory CD4+ T cells in Peyer's patches.

Background/Aims: Cytokine-induced neutrophil chemoattractant (CINC/gro), a member of interleukin-8 family, was found as a potent chemotactic factor for rat neutrophils. Although several chemokines have been shown to be potent regulators of T cell chemotaxis in vitro, the potential role of chemokines in T-cell migration in gut-associated lymphoid tissues has not been investigated in vivo. In the present study, the effects of CINC/gro on T-lymphocyte migration were examined in rat Peyer’s patches. Methods: T lymphocytes collected from intestinal lymph of rats were fluorescence-labeled and injected into the jugular vein. Peyer’s patches of the recipient rats were observed with intravital fluorescence microscopy and the effects of CINC/gro infusion was investigated. Lymphocyte flux in mesenteric collecting lymphatics was also observed. Results: In vivo infusion of CINC/gro significantly attenuated the initial lymphocyte interaction with postcapillary venules of Peyer’s patches. However, once these lymphocytes adhered to venules, CINC/gro treatment significantly accelerated the transendothelial migration of T lymphocytes and they also significantly increased their subsequent flux in collecting lymphatics. Conclusion: There is a possibility that CINC/gro could modulate the characteristics of T lymphocyte homing in the inflammatory sites of gut.

Although oral vaccination has numerous advantages over parenteral injection, degradation of the vaccine and low uptake by the gut associated lymphoid tissue (GALT) still complicate the development of efficient oral vaccines. However, previous studies in our laboratory demonstrated that chitosan microparticles can have suitable size, charge, loading and release characteristics for oral vaccination using ovalbumin as model vaccine. In this study, two different approaches were used to investigate the in vivo uptake of chitosan microparticles by murine Peyer's patches. Firstly, a confocal laser scanning microscopy (CLSM) study was performed to visualize the uptake of fluorescent-labeled chitosan microparticles in the Peyer's patches after intragastrical feeding. Subsequently, the intestinal epithelial uptake of ovalbumin loaded chitosan microparticles was visualized using immunohistochemical staining of ovalbumin. Because the microparticles are biodegradable, this entrapped ovalbumin will be released after intracellular digestion in the Peyer's patches. CLSM visualization demonstrated that chitosan microparticles enhance the uptake of fluorescent-labeled ovalbumin by the epithelium of the Peyer's patches. No ovalbumin uptake by the intestinal epithelium was observed when the protein was administered without microparticles. Moreover, immunohistochemical visualization studies revealed that ovalbumin could only be transported into the Peyer's patches after association to chitosan microparticles. Since uptake by Peyer's patches is an essential step in oral vaccination, these in vivo experiments demonstrate that chitosan microparticles are very promising vaccine delivery systems.

Development of apoptosis and changes in lymphocyte subsets were examined mainly by flow cytometer in thymus, mesenteric lymph nodes and Peyer's patches of mice up to 24 hours after oral inoculation with T-2 toxin (10 mg/kg). T-2 toxin attacked Peyer's patches first, then mesenteric lymph nodes, and finally thymus in relation to the course of enteric absorption of orally inoculated T-2 toxin. The degree of lymphocyte apoptosis was prominent in the thymus, moderate in the Peyer's patches, and somewhat mild in the mesenteric lymph nodes, suggesting the difference in lymphocyte population susceptible to T-2 toxin. As to the changes in lymphocyte subsets, CD4+ CD8+ T cells were most sensitive to T-2 toxin, and CD4+ CD8- T cells were more severely depressed than CD4- CD8+ T cells in the thymus. In the mesenteric lymph nodes, CD3+ cells was more clearly affected than CD19+ cells, and the numbers of CD4+ and CD8+ cells were similarly decreased. In the Peyer's patches, the numbers of CD3+, CD 19+, CD4+ and CD8+ cells were unexceptionally decreased. In addition, among IgM+, IgG+ and IgA+ B cells, the number of IA+ B cells which are more important in the mucosal immunity was most severely affected.

A plasmid encoding T1-SP10MN(A), a peptide derived from immunodominant regions of human immunodeficiency virus type 1 gp120, was delivered to rabbit Peyer’s patches using a helium- driven gene gun. Six weeks thereafter, 2 of 5 animals were given an intradermal booster immunization. Blood, feces, and vaginal washes were collected weekly and assayed by ELISA. High titer T1SP10MN(A) ‐ specific fecal and vaginal secretory IgA responses were observed, and the response appeared to be augmented following dermal booster immunizations. Specific serum IgG was also detected within 1 week of immunization and remained elevated through week 20 in the 2 animals receiving dermal boosts (titers ⁄6400). This study establishes the Peyer’s patch as a promising target tissue for DNA vaccination and demonstrates the efficacy of gene gun ‐ mediated delivery of foreign DNA to a mucosal tissue for the induction of an immune response. A human immunodeficiency virus (HIV) ‐ specific secretory Materials and Methods IgA (sIgA) response may reduce virus transmission at mucosal Animals. Specific pathogen‐free female New Zealand White surfaces through immune exclusion and other mechanisms [1]. rabbits (2.2‐2.5 kg) were purchased from Milbrook Farms (AmSeveral in vitro studies using mucosal immunizations have herst, MA). shown that HIV-specific neutralizing antibodies can be induced Plasmid vaccine construction. The nucleotide sequence encoding T1-SP10MN(A) was derived from the protein sequence

The transport of bovine serum albumin (BSA) across Peyer's patches (PP) was increased by conjugate synthesis with lectin concanavalin A (Con A). The transport of the intact form was increased by the conjugation and significantly reduced by colchicine. The increase is thought to be due to the endocytosis activity of PP in response to lectin Con A. The transport of the conjugate across the jejunal epithelium (JE) was also increased, and it was concluded that the increase was due to the increase in stability against enzymatic degradation. These results suggest that conjugate synthesis with lectin is an effective method to improve the poor absorption of polypeptides and protein drugs in the intestine.

BACKGROUND & AIMS: Recirculation of lymphocytes requires appropriate signals on the lymphocytes as well as the vascular endothelium. The aim of this report was to study the expression of the mucosal addressin required for Peyer's patch-selective lymphocyte homing during ontogeny of the murine intestine and investigate the role of this addressin in recirculation of mononuclear cells. METHODS: Immunohistochemistry and murine intestinal isografts were used in which the small intestine from neonatal mice is implanted subcutaneously in mice with severe combined immunodeficiency disease. RESULTS: Expression of the mucosal addressin cell adhesion molecule 1 during murine intestinal ontogeny was detected from embryonic day 15 in developing gut and in adult Peyer's patches and lamina propria. Isografted intestine developed normally; it was not exposed to luminal contents but expressed the mucosal addressin cell adhesion molecule 1. Mononuclear cells recirculated to native and isografted intestine and recirculation was inhibited by monoclonal antibody to mucosal addressin in a regionally specific manner with greatest inhibition in the distal intestine. CONCLUSIONS: The mucosal vascular addressin is expressed early in ontogeny and can be detected in lamina propria in addition to Peyer's patches of the gut. The isograft not only developed into a morphologically normal intestine but also expressed differentiation antigens required for normal lymphoid homing to gut without exposure to luminal contents or lymphocytes. (Gastroenterology 1997 Apr;112(4):1241-9)

BACKGROUND The capacity to generate (interferon-gamma) IFN-gamma, a potent immunoregulatory and inflammatory cytokine, is low in neonates and deficient in patients with food allergy. METHODS We investigated the effect of IFN-gamma on antigen transport in the gut. In experiment I rat pups were randomized into two groups at the age of 14 days i.e., before gut maturation: Group IFN was given intraperitoneally recombinant rat IFN-gamma on days 14, 16, 18, 20. In experiment II, rats were randomized into two groups at the age of 26 days, i.e., after gut maturation: Group IFN received the IFN-gamma treatment on days 26, 28, 30, 32. Controls in both experiments received sterile saline. The absorption of horseradish peroxidase (HRP) across jejunal segments with and without Peyer's patches was studied in Ussing chambers on days 21 and 33 for experiments I and II, respectively. RESULTS In experiment I, the absorption of intact HRP across both types of segments was significantly increased in Group IFN compared to controls. The mean (95% confidence interval) rate of degraded HRP absorption across patch-containing segments in Group IFN was significantly greater than in controls, 4420 (3162-6179) ng.h-1.cm-2 in comparison to 1550 (633-3790) ng.h-1.cm-2; F = 8.96, p = 0.009. CONCLUSION IFN-gamma increases macromolecular transport before gut maturation particularly across Peyer's patches. This Peyer's patch-targeted effect can be important eliciting mucosal immune responses against dietary antigens early in life and aiding their immune exclusion.

Purpose. The potential of using lectin-modified polymerized liposomes as Peyer's patch targeted oral delivery vehicles was examined.

The purpose of this work was to determine if anti-amebic antibody producing cell responses could be elicited in Peyer's patches and spleen in mice locally or systemically immunized with glutaraldehyde-fixed trophozoites of Entamoeba histolytica (GFT). The animals were inoculated with either a single or four doses of GFT via intragastric, rectal, and intraperitoneal routes. The anti-amebic antibody producing cell responses were analyzed by a spot forming cell assay (ELISPOT). The kinetics of antibody response revealed that a single dose of GFT by any route evoked anti-amebic responses in Peyer's patches and spleen. Furthermore, antibody producing cells of the three major isotypes were produced in both Peyer's patches and spleen of the mice receiving four doses of GFT, by either local or systemic routes. Our results indicate that immunization with GFT can induce a considerable number of specific antibody producing cells, which seem to remain in the Peyer's patches. After rectal and intraperitoneal immunization, females produced higher anti-amebic responses than males. Since either local or systemic immunization with GFT elicits both mucosal and systemic anti-amebic responses, this strategy should be considered as a promising tool for future elaboration of an anti-amebic vaccine.

The intermediate filaments of the dome epithelium of porcine Peyer's patches were studied by immunohistochemistry. The labelling patterns of monospecific antibodies directed against cytokeratins 8, 18 and 19 differed considerably. About 40% of the dome epithelial cells were intensely labelled by three different anti-cytokeratin 18 antibodies, indicating that large amounts of cytokeratin 18 are present in these cells. In order to verify that these cytokeratin-18-immunoreactive cells were M-cells, uptake studies using fluorescein-labelled yeast particles were performed. Numerous yeast particles were found exclusively in dome epithelial cells that were highly positive for cytokeratin 18, thus representing M-cells. In contrast, the content of cytokeratin 19 in M-cells was lower than that in neighbouring enterocytes. The labelling intensity of cytokeratin 8 did not differ between M-cells and enterocytes. In addition, the absence of vimentin and desmin from the dome epithelium of porcine Peyer's patches was demonstrated. The results show (1) that porcine M-cells differ from enterocytes in the composition of their cytoskeleton, (2) that cytokeratin 18 is a useful marker for detecting porcine M-cells and (3) that this marker directly correlates with M-cell function.

A total of 122 immunoglobulin (Ig)A-producing hybridoma clones were isolated from the Peyer's patches of vomitoxin-fed BALB/c mice and the resultant antibodies were characterized for their antigenic specificity and pathogenic potential. When reactivity was tested against a panel consisting of DNA, sphingomyelin, thyroglobulin, collagen, casein, cardiolipin and bovine serum albumin conjugates of phosphorylcholine, inulin and trinitrophenol that were representative of self and non-self antigens, approximately 95% of the monoclonal IgAs bound to at least one of the panel antigens and 80% bound to more than one antigen. The polyspecificity of some of the monoclonal IgAs was further suggested by demonstrating the capacity of one antigen to inhibit binding of monoclonal IgA to another antigen. Protein staining and Western blotting of gradient native polyacrylamide gels, indicated that trimeric IgA predominated in the isolated monoclonal IgAs. Repeated injections of mice with representative monoclonal IgAs induced microhaematuria in three of four of the clones tested but not IgA deposition in the kidney glomerulus. In addition, three of the four monoclonal IgAs caused IgG and C3 deposition in the kidney mesangium. These and previous results suggest that dietary vomitoxin promotes the polyclonal activation and expansion of IgA-secreting B cells at the Peyer's patch level and that resultant polyspecific, autoreactive IgA may contribute to kidney pathogenesis.

The permeability of peptides across rabbit jejunal epithelium (JE) and Peyer’s patches (PP) was compared. Kyotorphin (L-tyrosyl-L-arginine) was almost completely hydrolyzed during its membrane transport in both PP and JE, but [D-Arg2] Kyotorphin (L-tyrosyl-D-arginine) was less hydrolyzed in PP than in JE. Since the permeability of intact [D-Arg2] Kyotorphin was almost equal in PP and JE, no superiority of PP to JE was found for dipeptide transport. More intact fluorescein isothiocyanate (FITC)-labeled bovine serum albumin (FITC-BSA) and concanavalin A (FITC-Con A) were transported in PP than in JE. At both absorption sites, the transport of the intact FITC-Con A was superior to that of the intact FITC-BSA. Colchicine significantly reduced the total transport of the intact and degradation forms of both peptides and the reduction ratio was greater in PP than in JE. Accordingly, it was suggested that PP can be used as prominent absorption sites for polypeptides since they have lower peptidase activity and higher endocytosis activity than JE.

We compared the phenotypic characterization of antibody-secreting cells in the liver, the spleen, and Peyer's patch that had been subjected to various treatments in mice. The highest proportion of IgA-secreting cells was found in the liver mononuclear cells (MNC). They contained IgM-secreting cells in similar proportions to those in Peyer's patch but at lower proportions than in the spleen. In immunized mice, levels of IgG-secreting cells in the spleen and the liver were about 10 times higher than those in normal mice. The distribution pattern of immunoglobulin-secreting cells in Peyer's patch was virtually unchanged by any treatment. In the normal mice there were no significant differences among these organs in the distribution of the surface immunoglobulin phenotype in MNC. IgA-secreting cells in Peyer's patch secreted more antibodies per cell than those in the spleen or the liver.

Antibodies to the cytosolic leucocyte L1 protein (or calprotectin) were examined for reactivity with macrophages, neutrophils, and eosinophils identified by paired immunofluorescence staining in sections of normal human ileal mucosa, including Peyer's patches. Macrophages were recognised by expression of the myelomonocytic antigen CD68 (monoclonal antibody KP1). Neutrophilic granulocytes were identified by their content of neutrophil elastase, and eosinophilic granulocytes by monoclonal antibody EG2. Virtually all CD68+ macrophages in normal lamina propria and Peyer's patches were L1- and the same was true for most extravasated macrophages in normal peripheral lymph nodes. Some mesenteric lymph nodes, however, and all peripheral lymph nodes with overt pathological processes (malignant lymphoma) contained many CD68+L1+ macrophages. Numerous L1+ cells were also localised to the crypt region and to some extent beneath the villous epithelium in normal lamina propria, but they were mainly identified as EG2+ eosinophils. Such cells were remarkably scarce or absent beneath the follicle associated epithelium in the dome region of Peyer's patches, where CD68+L1- macrophages were abundant. Also subepithelial and interfollicular CD68- interdigitating dendritic cells in Peyer's patches (recognised by antibody to S-100 protein) were usually unreactive with L1 antibody. The L1 protein shows a broad spectrum of antimicrobial activities in vitro, and its putative antiproliferative properties are interesting in relation to the immunosuppression postulated to take place in lamina propria. The virtual absence of L1 producing cells beneath the follicle associated epithelium in Peyer's patches may support the immunostimulatory function of these macrophage rich structures, which are held to be crucial for induction of specific mucosal immunity.

The mechanisms of intercommunication between the immune and nervous systems are not fully understood. In the case of the intestine, the enteric nervous system is involved in the regulation of immune responses. It was therefore decided to employ immuno-histochemical techniques to investigate the structural organization of the enteric nervous system in Peyer's patches of the porcine small intestine. Using antibodies against various nervous system-specific markers (protein gene product 9.5, neuron-specific enolase, neurofilament 200, S-100 protein and the glial fibrillary acidic protein), an intimate and specific structural association could be demonstrated between enteric nerves and the compartments of Peyer's patches: follicles, interfollicular regions and domes. Peyer's patches have a close topographical relationship to the two submucosal plexuses. Enteric nerves are located around the follicle in the interfollicular area--the so-called "traffic area"--and in the dome area, which plays an important role in the uptake and presentation of antigens.

The effect of deprivation of Peyer's patches (PP) on transport of lymphocytes through intestinal lymph and intestinal mucosal immune responses was investigated in rats. All visible PP in the rat small intestine were excised in order to examine the roles of PP in the intestinal lymphatic system and mucosal immune responses of the intestine. Two weeks after the experimental excision of PP, lymphocyte transport in intestinal lymph was significantly decreased in PP-excised rats without significant changes in lymphocyte subsets as compared with sham operated control rats. Lymphocyte subsets as determined morphometrically in the intestinal mucosa showed no significant alteration in PP-excised rats. There was a significant decrease in the number of immunoglobulin A (IgA) containing cells in the intestinal mucosa of PP-excised rats, while IgM and IgG containing cells showed no statistically significant changes in number. Conversely, the macrophages in the intestinal mucosa increased in number, suggesting the enhanced accessory functions of these macrophages. Antigen-specific immune response was further studied in PP-excised rats using intraduodenal priming and challenge with cholera toxin (CT). Both the determinations of cells producing antigen-specific antibody in the intestinal mucosa using anti-CT antibody and those of cells secreting anti-CT Ig in the intestinal lymph by enzyme-linked immunospot (ELISPOT) assay showed a significant reduction of CT-specific antibody production in PP-excised rats compared with controls. Peyer's patches appear to have an important role in lymphocyte transportation through intestinal lymph and also in mucosal immune responses.

Peyer's patch have been extensively studied as a major inductive site for mucosal immunity within the small intestine. The intestinal mucosa contains numerous dendritic cells, which induce either protective immunity to infectious agents or tolerance to innocuous antigens, including food and commensal bacteria. Although during the past few years, several subsets of human mucosal dendritic cells have been described, a precise characterization of the different mouse mucosal dendritic cells subpopulations remains to be achieved with regard to their phenotype and localization in Peyer's patch. In this report, we have investigated by immunofluorescence on cryosection and by flow cytometry, the phenotype and the localization of dendritic cells into Peyer's patch of C57Bl/6 mouse intestine using dendritic cells markers. Positive and double staining for CD11c and BDCA-2, pDC/IPC, DC-LAMP, DC-SIGN, TLR8 and Langerin have been observed revealing new mouse intestinal DC subsets. This study provides new insight in the understanding of mucosal immune responses induced by natural processes as infections but also new perspectives for the evaluation of oral vaccines.

Some lactic acid bacteria (LAB) are known as representative of probiotics. To screen LAB effective to enhance intestinal immunity, in the present study, we developed an accurate and convenient in vitro evaluation system using Peyer's patch cells (PP-cells) isolated from the mice intestine. We observed that the amount of immunoglobulin A (IgA) produced by PP-cells co-cultured with LAB was well correlative to that in PP-cells, intestine and feces isolated from live mice after oral administration of LAB [correlation coefficient (r)=0.888, 0.883, and 0.920, respectively]. In addition, using this in vitro system, we suggest that the IgA level of PP-cells co-culturing with plant-derived LAB might be more enhanced than with animal-derived LAB.

Lymphocytes express integrin receptors, termed lymphocyte Peyer's patch high endothelial venule (HEV) adhesion molecules (LPAMs), that mediate their organ-specific adhesion to specialized HEVs found in mucosal lymphoid organs (Peyer's patches). LPAM-1 consists of a murine integrin alpha 4 noncovalently associated with integrin beta p. Here, we describe the cloning and expression of a mouse cDNA encoding beta p, which is an 806-amino acid transmembrane glycoprotein. The genomic Southern blot analysis indicates that beta p is the murine homologue of human beta 7. The function of alpha 4 beta 7 as a Peyer's patch-specific adhesion molecule was tested directly by expression of the murine beta 7 cDNA in an alpha 4+ beta 7-B-cell line or coexpression of the alpha 4 and beta 7 cDNAs in an alpha 4-beta 7-T-cell line. The transfected cells exhibited a new Peyer's patch-specific adhesive phenotype that could be specifically blocked by monoclonal antibodies against alpha 4 and beta 7. Moreover, an anti-beta 7 monoclonal antibody specifically blocked binding of normal lymphocytes to Peyer's patch HEV but did not inhibit their binding to peripheral lymph node HEVs, indicating that beta 7 is a unique component of the Peyer's patch-specific homing receptor.

The distribution patterns of extracellular matrix elements were determined to ascertain whether they play a role in the localization of lymphocytes in discrete T-cell, B-cell and dome antigen-processing domains within Peyer's patches. Antibodies against collagen types I, III and IV, laminin and fibronectin were applied to cryosections of mouse Peyer's patches and localized by direct or indirect immunoperoxidase methods. T-cell domains were identified with a monoclonal antibody against Thy-1.2. Labeled reticular fibers in distinctive patterns were more numerous in parafollicular and dome areas than within follicles. Germinal centers contained few such fibers. In parafollicular areas, fibers were oriented predominantly toward follicle domes; their distribution corresponded to T-cell zones and lymphocyte traffic areas, with their orientation being parallel to the migration pathways of lymphocytes from high endothelial venules to the antigen-processing domes. Subepithelial and subendothelial basal laminae were immunopositive for type-IV collagen, laminin and fibronectin. The dome subepithelial basal lamina had pore-like discontinuities through which lymphocytes migrated to and from the epithelium. The correspondence of the distribution patterns of extracellular matrix to specific functional domains of Peyer's patches suggests that this matrix provides a structural framework for lymphocyte migration and localization.

The objectives of this study were (a) to compare the aminopeptidase activity in the Peyer's patches of the jejunum and ileum of the albino rabbit against that in the adjacent patch-free segments and (b) to determine the relative sensitivities of the aminopeptidase activity in the Peyer's and non-Peyer's patches to aminopeptidase inhibitors and penetration enhancers. The results indicated that the Peyer's patches were about equal in aminopeptidase activity in the jejunum and in the ileum but were only 20-30% as rich in aminopeptidase activity as their neighboring patch-free areas. Compared to non-Peyer's patches, the aminopeptidase activity in the Peyer's patches was not as sensitive to the inhibitory effect of amastatin. It was, however, much more sensitive to the inhibitory effect of puromycin and p-chloromercuribenzoate and was somewhat more sensitive to the inhibitory effect of Na deoxycholate, Na glycocholate, and polyoxyethylene-9-lauryl ether. Therefore, based on substrate preferences and on the relative sensitivity of aminopeptidase activity to inhibition by aminopeptidase inhibitors and penetration enhancers, the relative proportions of various aminopeptidases in the Peyer's patches and in the non-Peyer's patches are likely different.

Lymphoid follicles from the sheep ileal Peyer's patch (PP) were used to prepare a cell suspension consisting of 98% surface IgM-positive (sIgM+) B cells and 1% T cells. Co-stimulation of follicular cells with pokeweed mitogen and either recombinant bovine interleukin 1 (IL 1) or IL 2 resulted in a marked proliferative response. In contrast, the addition of soluble F(ab')2 rabbit anti-sheep Ig completely inhibited the proliferative response induced by pokeweed mitogen and IL 1 or IL 2 co-stimulation. Anti-Ig inhibition of B cell proliferation was specific for ileal PP follicular cells and was not observed with mesenteric lymph node cells or splenocytes. Furthermore, suppression of ileal PP follicular B cell proliferation required at most divalent cross-linking of sIg was independent of Fc receptors, but was dependent on the concentration of anti-Ig and required 48 h for maximal effect. Negative signaling by sIgM indicates that ileal PP follicular B cells are functionally distinct from B cells in other secondary lymphoid tissues. Also, the present observations are consistent with previous reports indicating that B cell proliferation in ileal PP follicles is antigen independent.

Intravenously injected sheep antilaminin immunoglobulin G conjugated with horseradish peroxidase uniformly labeled the basement membrane of mouse villus epithelium but not that of Peyer's patch follicle domes, although laminin is abundant in both. This suggested differences in the permeability of capillaries underlying these epithelia. Therefore, the fine structure of mouse subepithelial villus and follicle capillaries and their permeability to selected macromolecules was compared. Fenestrae, abundant in villus capillaries, were extremely rare in dome capillaries as assessed by electron microscopy of tissue sections and freeze-fracture replicas. Two minutes after IV-injected horseradish peroxidase and 9 minutes after IV-injected hemoglobin, reaction product decorated the pericapillary space of 97% and 95%, respectively, of capillary profiles in the upper half of villi but only 28% and 2%, respectively, of capillary profiles in the upper half of patch domes. Reaction product was intense surrounding most villus capillaries but, when present, was faint in dome capillary adventitia. These results indicate that most subepithelial capillaries in mouse Peyer's patch domes, unlike those in villi, generally lack endothelial fenestrae, and the dome capillary network is less permeable to some macromolecules than that of the villus.

Ileal Peyer's patches (IPPs) in the sheep are composed of tightly packed follicles in which surface IgM-positive B cells proliferate and can be exported to the periphery. We report that the light chain rearrangement pattern in a single IPP follicle is much more restricted than in the entire tissue, which indicates that, as in the chicken bursa, ongoing rearrangement does not take place in this organ. Moreover, we show that B cells extensively diversify their antigen receptor while proliferating in IPP follicles. Sequencing of part of the V lambda locus indicates that this diversification is not achieved by gene conversion, but rather by untemplated somatic mutation and intense selective pressure. These results strongly imply that sheep IPPs behave as a bursa-equivalent, primary lymphoid organ of diversification and that somatic point hypermutation, which is known to proceed during secondary immune responses, can also generate an antibody repertoire.

The effect of orally administered SSG, a β -1,3-glucan obtained from the culture filtrate of a fungus, Sclerotinia sclerotiorum IFO 9395, on the function of Peyer's patch (PP) cells was investigated in comparison with that on spleen cells in mice. Oral administration of SSG enhanced the proliferative response of PP cells to a T-cell mitogen, concanavalin A (Con A), and a B-cell mitogen, lipopolysaccharide (LPS), although the response of spleen cells was not affected. Peyer's patch cells taken from mice which had received oral administration of SSG two days before, showed enhanced plaque-forming cell (PFC) response to sheep red blood cells (SRBC) after antigen (SRBC) stimulation for 5 days in vitro . These results suggest that oral administration of SSG can modulate the mucosal immune response.

Macrophages in Peyer's patches are important in the initiation of gastrointestinal immune responses to enteric pathogens. To examine their potential role in giardiasis, murine mononuclear cells were isolated from collagenase-treated Peyer's patches by their adherence to glass. These cells were incubated with Giardia lamblia trophozoites in the presence of nonimmune or immune (anti-Giardia antibody titer, greater than or equal to 1:1,024) mouse serum. Macrophages ingested trophozoites at low levels when they were incubated with nonimmune mouse serum. Ingestion was significantly increased at all time points (P less than 0.01) when cells and parasites were incubated in 5% immune mouse serum; the number of Giardia trophozoites ingested per 100 macrophages was 21.6 +/- 7.1 (standard error of the mean) at 1 h and increased to 59.0 +/- 16.4 at 8 h. Electron microscopy documented trophozoite destruction within macrophages. Association of G. lamblia with macrophages elicited an oxidative response; 50.9 +/- 3.6% of macrophages with trophozoites attached or ingested reduced the dye Nitro Blue Tetrazolium, compared with 13.0 +/- 5.2% for cells without associated trophozoites (P less than 0.04). These results demonstrate that macrophages are capable of ingesting G. lamblia in vitro and may play an important role in host defense in giardiasis.

The effects of Peyer's patch (PP) inactivation on local and systemic immune response in rats was investigated. A cauterization method has been developed to inactivate PP. Animals were primed intraperitoneally or intragastrically with trinitrophenyl-keyhole limpet haemocyanin (TNP-KLH) one day before cauterization, and were challenged intraintestinally two weeks later. The secondary immune response in the spleen, mesenteric lymph node (MLN) and intestinal villi was studied by immunohistochemistry. Histological observations on PP after inactivation showed that most T cells in the interfollicular area had disappeared, as had B cells in the follicle. T cells repopulated PP much slower than B cells. Complete recovery of PP occurred no earlier than 2 weeks after inactivation. The immunization experiments revealed higher numbers of anti-TNP antibody-forming cells (anti-TNP AFC) of IgM, IgG and IgA isotypes in the spleen of the PP-inactivated animals than in the controls. Very few anti-TNP AFC were found locally in the lamina propria of the intestinal villi or in the MLN in both groups. It is suggested that PP playa role in the regulation of systemic immune responses against intestinally-administered thymus-dependent antigen. Moreover, inactivation of PP could alter the antigen uptake by gut epithelium and the local antigen processing. As a result, an increased amount of antigen could reach the spleen eliciting a higher immune response.

Carbonic anhydrase cytochemistry of the ileal Peyer's patch in foetal and neonatal lambs has indicated secretion from the follicle-associated epithelium to the follicles. Reaction for carbonic anhydrase in the follicle-associated epithelium was found in the luminal plasma membrane, in cytoplasmic vesicles, and in vacuoles containing 50-nm membrane-bounded particles that seemed to be shed to the intercellular space. The lateral plasma membrane was negative for carbonic anhydrase, indicating that formation of carbonic anhydrase-positive particles was restricted to vacuoles. Administration of ferritin to ileal loops of sheep foetuses showed ferritin localized in vesicles and vacuoles of the follicle-associated epithelium followed by exocytosis, together with carbonic anhydrase-positive particles, into the indentations of the lateral cell border. The carbonic anhydrase-positive particles seemed to be transported to the centres of lymphoid follicles where many were attached to the plasma membrane of lymphocytes. Carbonic anhydrase-positive particles were also seen in vesicles and sometimes free in the cytoplasm of the lymphocytes or attached to their nuclear envelope. Light microscopically, carbonic anhydrase reactivity of the follicle-associated epithelium was associated with the early formation of the ileal Peyer's patch at about 100 days gestation. At this time the follicle-associated epithelium showed a strong luminal but at most a weak lateral staining. With further foetal development there was a progressive increase in the amount of carbonic anhydrase-positive reaction product in extracellular particles, both along the lateral cell borders of the follicle-associated epithelium and among the lymphocytes of the follicle centres.

Prolonged dietary exposure of mice to the trichothecene vomitoxin induces abnormally high levels of serum IgA and kidney mesangial IgA accumulation in a manner that is highly analogous to the human glomerulonephritis IgA nephropathy. In this study, the capacity of Peyer's patch and splenic lymphocytes to produce IgA and IgG were compared in B6C3F 1 mice that were fed diets with and without 25 ppm vomitoxin for up to 12 wk. Serum IgA increased 2-,4- and 8-fold after 4, 8 and 12 wk, respectively, of vomitoxin exposure and it became the primary serum isotype, whereas serum IgG was unaffected. On termination of the experiment there were increased numbers of IgA-secreting cells in Peyer's patches after 8 wk of toxin exposure and in the spleen after 4, 8 and 12 wk of toxin exposure. There were also increased numbers of IgG-secreting cells in Peyer's patches on termination of the experiment at 4, 8 and 12 wk but no effect was observed in the spleen. Supernatant IgA and IgA-secreting cell numbers were also markedly elevated in lymphocyte cultures obtained from Peyer's patches and, to a lesser extent, from spleens of treated mice compared with controls. Based on output of treated mice relative to corresponding controls, IgA secretion was greatest in concanavalin-A-stimulated and unstimulated Peyer's patch cultures. Enhanced IgG secretion and IgG-secreting cells were also observed in mitogen-stimulated and unstimulated Peyer's patch lymphocyte cultures of treated relative to control mice, but differences in splenocyte cultures were negligible. Based on total Ig output, IgA production was 8- to 20-fold greater than IgG production in both control and treatment Peyer's patch cultures. In contrast, vomitoxin treatment caused a shift from primarily IgG production in lipopolysaccharide-stimulated spleen cultures to equivalent IgA production. These data provide in vitro evidence that ingestion of vomitoxin promotes terminal differentiation of IgA-secreting progenitors in the Peyer's patch and, to a lesser extent, in the spleen. These functional changes are consistent with the shift from IgG to IgA as the primary serum isotype.

The aim of this study was to determine the role of CD4 and CD8 cells on specific antibody production by murine Peyer's patch (PP) cells after oral immunization with Actinomyces viscosus in mice. Female DBA/2 mice were orally immunized with three low doses of heat-killed A. viscosus. Sham-immunized mice served as a control group. Mice were depleted of CD4 or CD8 cells by intraperitoneal injection of anti-CD4 or anti-CD8 antibodies daily for 3 days before oral immunization. One week after the last oral immunization, PPs were removed and cell suspensions were cultured with A. viscosus. Specific antibody production in the culture supernatants was assessed by enzyme-linked immunosorbent assay. The results showed that oral immunization with A. viscosus induced a predominant specific immunoglobulin A (IgA) response by PP cells and, to a lesser extent, IgM antibodies. Depletion of CD4 but not CD8 cells suppressed the production of specific antibodies. These results suggest that oral immunization with low doses of A. viscosus may induce the production of specific antibodies by murine PP cells in a CD4-cell-dependent fashion.

Intestinal allergic diseases are initiated by aberrant Th2-type immune responses, including elevation of IgE antibodies (Abs) and infiltration of eosinophils. However, little is known about the role of Peyer's patches (PP) in the control of allergic diseases. Using a mouse model for food allergy, we here show that mice lacking PP are more susceptible to disease development and show higher levels of antigen-specific IgE Abs than do PP-intact mice. In our study, we noted that high numbers of eosinophils infiltrated into the small intestine of PP-null mice. In contrast, the PP of intact mice contained regulatory CD4+CD25+ Foxp3+ T cells (Treg) that are known to produce high levels of IL-10, and inhibited the development of allergic diarrhea. PP-intact mice thus developed allergic diarrhea when treated with anti-CD25 or anti-IL-10 monoclonal antibody (mAb) in vivo. These studies demonstrate that PP, as the site where IL-10-producing Treg cells are created, mediate the mucosal regulatory network for the control of undesired allergic responses in the intestine.

Long-term antibiotic administration is sometimes necessary to control bacterial infections during the perioperative period. However, antibiotic administration may alter gut bacterial flora, possibly impairing gut mucosal immunity. We hypothesized that 1 week of subcutaneous (SC) antibiotic injections would affect Peyer's patch (PP) lymphocyte numbers and phenotypes, as well as mucosal immunoglobulin A (IgA) levels.Sixty-one male Institute of Cancer Research mice were randomized to CMZ (cefmetazole 100 mg/kg, administered SC twice a day), IPM (imipenem/cilastatin 50 mg/kg x 2), and control (saline 0.1 mL x 2) groups. After 7 days of treatment, the mice were killed and their small intestines removed. Bacterial numbers in the small intestine were determined using sheep blood agar plates under aerobic conditions (n = 21). PP lymphocytes were isolated to determine cell numbers and phenotypes (CD4, CD8, alphabetaTCR, gammadeltaTCR, B220; n = 40). IgA levels in the small intestinal and bronchoalveolar washings were also measured with ELISA.Antibiotic administration decreased both bacterial number and the PP cell yield compared with the control group. There were no significant differences in either phenotype percentages or IgA levels at any mucosal sites among the 3 groups.Long-term antibiotic treatment reduces PP cell numbers while decreasing bacterial numbers in the small intestine. It may be important to recognize changes in gut mucosal immunity during long-term antibiotic administration.

The characteristics of the adhesion of PCC Lactobacillus fermentum VRI 003 to Peyer's patches was studied in vitro. The adhesion of L. fermentum 003 was strongly inhibited in the presence of d-mannose and methyl-alpha-d-mannoside although other carbohydrates tested, such as N-acetyl-glucosamine, d-galactose, d-glucose and l-fucose, did not affect the adhesion. Lactobacillus fermentum 003 was shown to strongly attach to mannose immobilized on a surface using BSA, suggesting that L. fermentum 003 specifically adhered to mannose-containing molecule(s). Pretreatment of L. fermentum 003 with proteinase K and trypsin decreased the adhesive capacity and bacterial surface extracts diminished adhesion of L. fermentum 003 indicating that cell surface proteins are involved in adhesion to Peyer's patches. It was concluded that a mannose-specific protein mediated adhesion of L. fermentum 003 to the Peyer's patches.

Freshly excised rat, ovine and bovine ileal Peyer's patch (PP) and non-Peyer's patch tissues (NPP) were mounted in modified horizontal polyethylene diffusion chambers with a range of window areas. Rat tissue was initially used to establish that barrier function and histology were maintained for up to 60 min. Horse-radish peroxidase (HRP) fluxes and S. Typhimurium adherence and invasion were significantly higher in rat PP over NPP. Particle uptake was shown to be a rapid, energy-, time-, and size-dependent process, occurring more readily in PP than NPP tissue in each species. In a kinetic analysis, particles were localized initially in the follicle-associated epithelium and then in the dome region. For NPP uptake, particles were initially localized to villous epithelium, and were then detected in the crypts and lamina propria. Electrophysiological parameters including pharmacologically-stimulated inward short-circuit current responses were determined in isolated PP and NPP from each species mounted under identical conditions in Ussing chambers. In conclusion, comparative functional and histological characteristics of PP from several species were demonstrated in horizontal diffusion chambers. Horizontal diffusion chambers are therefore a useful in vitro model in which a range of functions including transport of particulate formulations by PP may be examined.

The infection of mice with virulent and avirulent strains of Y. enterocolitica O: 8 resulted in polyclonal activation of the repertory of spleen and Peyer’s patches B lymphocytes, including some autoreactives clones.

Coeliac disease frequency increases by obscure reasons and affects in some Western countries as much as 1% of the populations. The second one of monozygotic twins does not develop the disease in 100% but only in 20-50%. To unravel these mysteries, literature was searched to determine the disease background and find suggestions for research and prevention. The causal antigen of coeliac disease is gluten of wheat that is neutralised in the intestine by secretory immune globulin A (sIgA). SIgA is secreted by the secondary (lymphoid) immune system that develops in a newborn infant after the primary (central) immune organs thymus and bone marrow have been primed with antigens of the intestine. Predisposed infants are sensitive for development of coeliac disease during the time without sIgA secretion into the intestine. The risk of the disease diminishes when sIgA cycles of gluten neutralisation develop. Peyer's patches (PP) of the secondary immune system play a central role in the cycles and possibly do not function well in the case of coeliac disease. Coeliac disease in predisposed infants may be prevented by delay of bread consumption till the time of normal sIgA secretion and by application of a challenge period with gluten (see Discussion). It is concluded that sIgA secretion into body cavities and malfunction of immune cells in PP should be included in the future research of coeliac disease as well as in more allergic diseases (type 1 diabetes, Crohn disease, asthma, hay fever). © 2005 Elsevier Ltd. All rights reserved.