ovalbumin and Trichinellosis

The recruitment of CD4+CD25+Foxp3+T (Treg) cells is one of the most important mechanisms by which parasites down-regulate the immune system.. We compared the effects of Treg cells from Trichinella spiralis-infected mice and uninfected mice on experimental allergic airway inflammation in order to understand the functions of parasite-induced Treg cells. After four weeks of T. spiralis infection, we isolated Foxp3-GFP-expressing cells from transgenic mice using a cell sorter. We injected CD4+Foxp3+ cells from T. spiralis-infected [Inf(+)Foxp3+] or uninfected [Inf(-)Foxp3+] mice into the tail veins of C57BL/6 mice before the induction of inflammation or during inflammation. Inflammation was induced by ovalbumin (OVA)-alum sensitization and OVA challenge. The concentrations of the Th2-related cytokines IL-4, IL-5, and IL-13 in the bronchial alveolar lavage fluid and the levels of OVA-specific IgE and IgG1 in the serum were lower in mice that received intravenous application of Inf(+)Foxp3+ cells [IV(inf):+(+) group] than in control mice. Some features of allergic airway inflammation were ameliorated by the intravenous application of Inf(-)Foxp3+ cells [IV(inf):+(-) group], but the effects were less distinct than those observed in the IV(inf):+(+) group. We found that Inf(+)Foxp3+ cells migrated to inflammation sites in the lung and expressed higher levels of Treg-cell homing receptors (CCR5 and CCR9) and activation markers (Klrg1, Capg, GARP, Gzmb, OX40) than did Inf(-)Foxp3+ cells.. T. spiralis infection promotes the proliferation and functional activation of Treg cells. Parasite-induced Treg cells migrate to the inflammation site and suppress immune responses more effectively than non-parasite-induced Treg cells. The adoptive transfer of Inf(+)Foxp3+ cells is an effective method for the treatment and prevention of allergic airway diseases in mice and is a promising therapeutic approach for the treatment of allergic airway diseases.

Topics: Adoptive Transfer; Alum Compounds; Animals; Asthma; Cytokines; Female; Forkhead Transcription Factors; Hypersensitivity; Mice; Mice, Inbred C57BL; Ovalbumin; T-Lymphocytes, Regulatory; Trichinella spiralis; Trichinellosis

We have previously found that co-immunisation with ovalbumin (OVA) and the body fluid of the helminth Ascaris suum inhibited an OVA-specific delayed type hypersensitivity (DTH) response by reducing OVA-specific CD4+ T lymphocyte proliferation via an IL-4 independent mechanism. In the present study, we determined whether parasite infections themselves could induce similar changes to peripheral immunisation by examining the modulation of OVA-specific immune responses during acute and chronic helminth infections. Surprisingly, an acute infection with Trichinella spiralis, but not a chronic infection with Heligmosomoides polygyrus, inhibited the OVA-specific DTH reaction. Correspondingly, the T helper 1 (Th1) OVA-specific response was decreased in mice infected with T. spiralis, but not with H. polygyrus. Inhibition of the Th1 response may be a result of a shift in the Th1/Th2 balance as although both H. polygyrus and T. spiralis infected mice induced a Th2 OVA-specific response, that exhibited by T. spiralis was more potent. Furthermore, although IL-10 secretion upon OVA restimulation was similarly increased by both infections, production of this immunoregulatory cytokine may play a role in the suppression of immune responses observed with T. spiralis infection depending on the context of its release. Interestingly, analysis of the OVA-specific T lymphocyte division by carboxyfluorescein diacetate succinimidyl ester (CFSE) staining revealed that gastro-intestinal infection with the acute helminth T. spiralis, but not with chronic H. polygyrus, inhibited the systemic immune response by significantly inhibiting the antigen-specific T cell proliferation during the primary response, a mechanism similar to that observed when A. suum parasite extracts were directly mixed with the OVA during immunisation in our previous studies.

Topics: Acute Disease; Adoptive Transfer; Animals; Antigens, Helminth; CD4 Lymphocyte Count; Chronic Disease; Female; Helminthiasis; Hypersensitivity, Delayed; Immune Tolerance; Intestinal Diseases, Parasitic; Mice; Mice, Transgenic; Models, Animal; Nematospiroides dubius; Ovalbumin; Strongylida Infections; Th1 Cells; Th2 Cells; Trichinella spiralis; Trichinellosis

Several studies demonstrate that intestinal mucosal mast cells (IMMC) are modulated by nervous reflexes as well as by intraluminal content. We recently demonstrated that peptones, such as ovalbumin hydrolysate (OVH), induce the release of rat mast cell protease II (RMCP II), indicating IMMC degranulation. The response is due to complex neuroendocrine reflexes. Somatostatin (SS) and its analogues have been used as potential treatments for inflammation in other body systems with contradictory results. The aim of this study was to evaluate if somatostatin could contribute to the reduction of intestinal mucosal mast cell degranulation. Anesthetized rats were prepared for duodenal perfusion and mast cell activation was measured by analysis of RMCP II concentration in the duodenal perfusate. Somatostatin significantly decreased RMCP II concentration in both nonstimulated conditions and after ovalbumin hydrolysate perfusion. However, when somatostatin was given previously to OVH, the peptone still induced a slight increase of RMCP II. Similar effects were observed in animals previously treated with capsaicin. These protocols were repeated in animals infected with Trichinella spiralis, which induces mucosal mast cell hyperplasia. In these cases, somatostatin blocked the effect of OVH, thus, preventing an increase in RMCP II concentration. Fresh frozen tissue sections from the duodenum were processed in an attempt to demonstrate the presence of SS receptors in mast cells using immunofluorescence and Fluo-peptide labeling techniques. Confocal images from duodenum specimens demonstrate the existence of SS receptors in positive cells for RMCP II. Taken together, these results indicate that somatostatin diminishes mast cell activity and in consequence could prevent the intestinal responses to mast cell hyperplasia.

Topics: Animals; Capsaicin; Cell Degranulation; Chickens; Duodenum; Fluorescent Antibody Technique; Hyperplasia; Intestinal Mucosa; Male; Mast Cells; Microscopy, Confocal; Ovalbumin; Peptones; Protein Hydrolysates; Rats; Rats, Sprague-Dawley; Receptors, Somatostatin; Serine Endopeptidases; Somatostatin; Trichinella spiralis; Trichinellosis

Although in vitro development of a Th2 response from naive CD4+ T cells is Stat6 dependent, mice immunized with a goat Ab to mouse IgD have been reported to produce a normal primary IL-4 response in Stat6-deficient mice. Experiments have now been performed with mice immunized with more conventional Ags or inoculated with nematode parasites to account for this apparent discrepancy. The ability of an immunogen to induce a primary in vivo IL-4 response in Stat6-deficient mice was found to vary directly with its ability to induce a strong type 2 cytokine-biased response in normal mice. Even immunogens, however, that induce strong primary IL-4 responses in Stat6-deficient mice induce poor memory IL-4 responses in these mice. Consistent with this, Stat6-deficient CD4+ T cells make relatively normal IL-4 responses when stimulated in vitro for 3 days with anti-CD3 and anti-CD28, but poor IL-4 responses if they are later restimulated with anti-CD3. Thus, Stat6 signaling enhances primary IL-4 responses that are made as part of a type 0 cytokine response (mixed type 1 and type 2) and is required for normal development or survival of Th2 memory cells.

Topics: Animals; Antibodies; Antibodies, Monoclonal; CD3 Complex; CD4-Positive T-Lymphocytes; Chickens; Female; Goats; Immunoglobulin D; Immunologic Memory; Injections, Intravenous; Interleukin-4; Intestinal Diseases, Parasitic; Male; Mast Cells; Mice; Mice, Inbred BALB C; Mice, Inbred C57BL; Mice, Knockout; Nematospiroides dubius; Nippostrongylus; Ovalbumin; Receptors, Interleukin-4; Signal Transduction; STAT6 Transcription Factor; Strongylida Infections; Th2 Cells; Trans-Activators; Trichinella spiralis; Trichinellosis

Guinea pigs were infected with Trichinella spiralis. A pooled serum from the infected guinea pigs was fractionated by DEAE-cellulose column chromatography and Sephadex G-200 gel filtration. An IgE-rich fraction was injected into rabbits. The antiserum from the rabbits, after appropriate absorption with a normal guinea pig plasma, formed a precipitin line in immunoelectrophoresis and in immunodiffusion against a guinea pig serum containing IgE antibodies to ovalbumin. Uptake of 125I ovalbumin was observed in radioimmunoelectrophoresis. This anti IgE could be used in enzyme-linked immunosorbent assay of IgE antibodies to ovalbumin.

Topics: Animals; Antibodies, Anti-Idiotypic; Enzyme-Linked Immunosorbent Assay; Guinea Pigs; Immunoenzyme Techniques; Immunoglobulin E; Immunologic Techniques; Ovalbumin; Trichinellosis

Antigens derived from Trichinella spiralis were used to challenge, in vitro, sensitized jejunum from infected guinea-pigs while monitoring ion transport properties of the tissue. Antigen challenge resulted in dose-dependent increases in trans-epithelial electrical potential difference and short circuit current. Both antigen-stimulated electrical alterations and Schultz-Dale contractions were demonstrated in small intestinal tissue after the passive transfer of immune serum containing anti-trichinella homocytotropic antibodies.

Topics: Anaphylaxis; Animals; Antigens, Helminth; Dose-Response Relationship, Immunologic; Electric Conductivity; Guinea Pigs; Hypersensitivity, Immediate; Immune Sera; Immunization, Passive; Intestinal Mucosa; Intestine, Small; Male; Membrane Potentials; Ovalbumin; Passive Cutaneous Anaphylaxis; Trichinellosis

Selective suppression of the total IgE antibody response has been achieved in rats by injection of rabbit anti-rat epsilon-chain antibodies. This IgE-specific suppression was maintained during the course of a natural infection by the nematode Trichinella spiralis. Depletion of the IgE antibody response resulted in a marked reduction of the number of eosinophils attracted to the T. spiralis larvae encysted in striated muscle. Blood eosinophilia following T. spiralis infection, although reaching normal peak levels, was abbreviated in IgE-suppressed animals. Moreover, IgE-depleted animals were more susceptible to the infection; they harbored two to three times more larvae encysted in their muscles than their control litter mates.

Topics: Animals; Antibody Specificity; Cytoplasmic Granules; Eosinophilia; Eosinophils; Female; Immunoglobulin E; Immunoglobulin epsilon-Chains; Immunosuppression Therapy; Mast Cells; Ovalbumin; Pregnancy; Rabbits; Rats; Trichinellosis

Infection of CFW mice with Trichinella spiralis induced a state of relative unresponsiveness to passive cutaneous anaphylaxis (PCA) induced with hen egg albumin and its corresponding antibodies. The unresponsiveness was to PCA produced either with immunoglobulin G1 (IgG1) or IgE type of antibodies, but was more pronounced with the latter. As few as 25 larvae given by stomach tube 20 days before induced this resistance, although 400 larvae induced a greater resistance. When 400 to 600 larvae were fed to mice, the refractoriness of these mice to PCA was noticed 15 days later. The sera of infected mice had the ability to inhibit mainly PCA induced by IgE. This inhibitory property of sera from infected mice was more pronounced 35 days after infection than 10 months later, when only weak inhibitory activity was detected. Purified rat IgE inhibited the PCA reactions induced in both mice and rats with mouse IgE-type antibody. At high concentrations, evidence of inhibition of the IgG1-induced PCA in mice was also obtained. We believe that the relative unresponsiveness of infected mice is due to an increase in production of IgE which competitively blocks the mast cell sites for other IgE molecules.

Topics: Animals; Dose-Response Relationship, Immunologic; Female; Immunoglobulin E; Immunoglobulin G; Male; Mice; Mice, Inbred C57BL; Myeloma Proteins; Ovalbumin; Passive Cutaneous Anaphylaxis; Rats; Time Factors; Trichinella; Trichinellosis