• Title/Summary/Keyword: oral tolerance

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Induction of Oral Tolerance to Japanese Cedar Pollen

  • Kim, Joung-Hoon;Mun, Yeun-Ja;Ahn, Seong-Hun;Park, Joung-Suk;Woo, Won-Hong
    • Archives of Pharmacal Research
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    • v.24 no.6
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    • pp.557-563
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    • 2001
  • Oral tolerance is thought to play a role in preventing allergic responses and immune-mediated diseases. An improved mouse model of the oral tolerance to Japanese cedar pollen (JCP) as antigen was developed in order to detect induction of the tolerance, and the immunological characteristics of this model were also elucidated. Oral tolerance was induced by C3H/ HeN mice given an oral administration of 10 mg JCP 7 days before immunization with an i.p. injection of 0.1 mg JCP in complete Freunds adjuvant (CFA). The effects of oral JCP on systemic immunity were assessed by enzyme-linked immunosorbent assay (ELISA) of immunoglobulin (Ig) levels in serum collected on day 7 or 14 after immunization. Oral tolerance to JCP was adequately induced on day 7 after immunization and was more effective in C3H/HeN mice than in BALB/c mice. The tolerance was primarily concerned with the decreased serum levels of antigen-specific IgG. In these mice, oral administration of JCP also suppressed various immune responses to the antigen including delayed-type hypersensitivity (DTH), total Igl level and anti-JCP IgGl level. The suppression of these immune responses by the oral antigen was associated with a significant reduction in interleukin-4 (IL-4) production. These findings therefore indicate that this C3H/HeN mice model has potential use in detecting the induction of oral tolerance by JCP and suggest that this tolerance model may be effective in the treatment and prevention of allergic responses caused by the antigen.

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Oral Tolerance: Not Simple But more Complex

  • Chung, Yeonseok;Kang, Chang-Yuil
    • IMMUNE NETWORK
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    • v.3 no.3
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    • pp.169-175
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    • 2003
  • The intestinal immune system can discriminate between harmful and unharmful antigens and do not provoke productive immunity to unharmful antigen. Thus oral administration of antigen is one of classical methods for inducing antigen-specific immune tolerance in the periphery. Furthermore, oral tolerance has been investigated for the treatment of autoimmune disorders in human clinical trials. However, the detail mechanism of oral tolerance and contributing factors are not defined clearly at this time. Recent studies demonstrate unique types of immune cell that suppressing immune response, such as regulatory T cell and tolerogenic dendritic cell. This article reviews the factors involved in oral tolerance and discusses our current understanding base on the recent literatures and our works.

Cholera Toxin Disrupts Oral Tolerance via NF-κB-mediated Downregulation of Indoleamine 2,3-dioxygenase Expression

  • Kim, Kyoung-Jin;Im, Suhn-Young
    • Biomedical Science Letters
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    • v.23 no.3
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    • pp.175-184
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    • 2017
  • Cholera toxin (CT) is an ADP-ribosylating bacterial exotoxin that has been used as an adjuvant in animal studies of oral immunization. The mechanisms of mucosal immunogenicity and adjuvanticity of CT remain to be established. In this study, we investigated the role of indoleamine 2,3-dioxygenase (IDO), which participates in the induction of immune tolerance, in CT-mediated breakdown of oral tolerance. When IDO-deficient ($IDO^{-/-}$) mice and their littermates were given oral ovalbumin, significant changes in antibody responses, footpad swelling and $CD4^+$ T cell proliferation were not observed in $IDO^{-/-}$ mice. Feeding of CT decreased IDO expression in mesenteric lymph nodes (MLN) and Peyer's patch (PP). CT-induced downregulation of IDO expression was reversed by inhibitors of nuclear factor-kappa B (NF-${\kappa}B$), pyrrolidine dithiocarbamate and p50 small interfering RNA. IDO expression was downregulated by the NF-${\kappa}B$ inducers lipopolysaccharide and tumor necrosis factor-${\alpha}$. CT dampened IDO activity and mRNA expression in dendritic cells from MLN and PP. These data indicate that CT disrupts oral tolerance by activating NF-${\kappa}B$, which in turn downregulates IDO expression. This study betters the understanding of the molecular mechanism underlying CT-mediated abrogation of oral tolerance.

Immunological Properties of Orally Induced Tolerance in Long-term Administered Mice with Casein (Casein을 장기간 섭취한 마우스에서 유도된 경구관용의 면역하적 특성)

  • 김순미
    • Journal of Nutrition and Health
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    • v.27 no.10
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    • pp.979-987
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    • 1994
  • We have examined the antigen specificity in orally tolerant mice fed with the casein(CN) diet. In contrast to previous reported results of studies on oral tolerance, these mice responded poorly to ovalbumin(OVA) and ovomucoid(OM), as well as $\alpha$sl-enriched fraction of these cells suppressed anti $\alpha$sl-CN antibody production of naive mice, but could not significantly suppressed antibody response of previously immunized recipient mice. These results indicate that oral tolerance was not medicate through suppressor T cell activities.

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Oral Tolerance Increased the Proportion of CD8+ T Cells in Mouse Intestinal Lamina Propria

  • Cho, Kyung-Ah;Cha, Je-Eun;Woo, So-Youn
    • IMMUNE NETWORK
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    • v.8 no.2
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    • pp.46-52
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    • 2008
  • Background: Oral tolerance is defined by the inhibition of immune responsiveness to a protein previously exposed via the oral route. Protein antigens exposed via the oral route can be absorbed through the mucosal surfaces of the gastrointestinal tract and can make physical contact with immune cells residing in the intestinal lamina propria (LP). However, the mechanisms of oral tolerance and immune regulation in the intestines currently remain to be clearly elucidated. Methods: In order to determine the effect of oral protein antigen intake (ovalbumin, OVA) on the intestinal LP, we assessed the expression profile of the T cell receptor and the co-receptors on the cells from the intestines of the tolerant and immune mouse groups. Results: We determined that the proportion of OVA-specific B cells and ${\gamma}{\delta}$ T cells had decreased, but the CD8${\alpha}{\beta}$ and D8${\alpha}{\alpha}$ T cells were increased in the LP from the tolerant group. The proportion of CD8+ T cells in the spleen did not evidence any significant differences between treatment groups. Conclusion: These results indicate that CD8+ T cells in the intestinal LP may perform a regulatory role following antigen challenge via the oral route.

Induction of Immunological Tolerance by Treatment of Ginseng Extract (인삼 엑기스의 경구 면역 관용에 관한 연구)

  • 배만종
    • The Korean Journal of Food And Nutrition
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    • v.9 no.2
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    • pp.176-180
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    • 1996
  • In order to develop new bioactive functions ginseng extract, it was studies whether the ginseng extracts on the induction of immunological tolerance In mice. Oral immunologic tolerance was induced by the secondary exposure of egg albumin + alum following gastrointestinal exposure nth egg albumin In mice, and the effect on anti EA antibody in blood, 7 cell subset in spleen were Investigated. The results obtained were as follows. EA group and EA + GE group was capable of conferring tolerance, contained a profound for 5 weeks experimental but saline group restricted to induce tolerance. GE group did not show the activity of tolerance by the first immunogens exposure, but induced the tolerance by the secondary exposure. And also spleen T cells, CD 8+ and CD 4+ were decreased. These results suggested that ginseng may affect the induction of immunological tolerance, which may be associated proliferative response of CD 4+ and CD 8+ in splenocyte.

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Expression of Co-stimulatory Molecules and STAT/SOCS Signaling Factors in the Splenocytes of Mice Tolerized against Arthritis by Oral Administration of Type II Collagen (제2형 콜라겐으로 경구관용을 유도한 관절염 모델 마우스의 비장림프구내의 보조자극인자 및 STAT/SOCS 신호전달 인자의 발현 양상조사)

  • Lee, Kang-Eun;Hwang, Sue-Yun;Min, So-Youn;Kim, Ho-Youn
    • IMMUNE NETWORK
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    • v.3 no.3
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    • pp.248-254
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    • 2003
  • Oral administration of antigen has long been used in the induction of immune tolerance in various animal models of autoimmune diseases including rheumatoid arthritis (RA). Alleveation of arthritogenic symptoms has been reported from RA patients who received oral administration of type II collagen (CII) without side effects, however its rather inconsistent therapeutic efficacy and variation among patients calls for more detailed investigation on the mechanism of oral tolerance to be settled as regular treatment for RA. In an attempt to understand the immunogenic processes underpinning tolerance induction by orally administered CII, we analyzed changes in the expression of costimulatory molecules and STAT/SOCS signaling messengers in the mouse model of collagen induced arthritis (CIA). We found thatin the spleen of CIA mice, that has been undergone repeated oral feeding of CII prior to the induction of arthritis, showed increased promortion of CTLA4 expressing lymphocytes than in the spleen of PBS fed control. On the other hand, cells expressing CD28 or ICOS were decreased in the spleen of tolerized mice. Tolerance induction by oral CII administration also enhanced the expression of STAT6 in both RNA and protein level, while not affecting the expression of STAT3. The expression of SOCS3, which hasbeen known to transmit STAT-mediated signals from Th2 type cytokines, remained unchanged in the spleen of tolerized mice. Interestingly transcript of SOCS1, which has been associated with Th1 related pathways, was only visible in the spleen of tolerized but not of control mice, suggesting that as in the case of IL-6 signaling, it may exert a feed back inhibition toward the Th1 type stimulation.

Expression of Cholera Toxin B Subunit and Assembly as Functional Oligomers in Silkworm

  • Gong, Zhao-Hui;Jin, Hui-Qing;Jin, Yong-Feng;Zhang, Yao-Zhou
    • BMB Reports
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    • v.38 no.6
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    • pp.717-724
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    • 2005
  • The nontoxic B subunit of cholera toxin (CTB) can significantly increase the ability of proteins to induce immunological tolerance after oral administration, when it was conjugated to various proteins. Recombinant CTB offers great potential for treatment of autoimmune disease. Here we firstly investigated the feasibility of silkworm baculovirus expression vector system for the cost-effective production of CTB under the control of a strong polyhedrin promoter. Higher expression was achieved via introducing the partial non-coding and coding sequences (ATAAAT and ATGCCGAAT) of polyhedrin to the 5' end of the native CTB gene, with the maximal accumulation being approximately 54.4 mg/L of hemolymph. The silkworm bioreactor produced this protein vaccine as the glycoslated pentameric form, which retained the GM1-ganglioside binding affinity and the native antigenicity of CTB. Further studies revealed that mixing with silkworm-derived CTB increases the tolerogenic potential of insulin. In the nonconjugated form, an insulin : CTB ratio of 100 : 1 was optimal for the prominent reduction in pancreatic islet inflammation. The data presented here demonstrate that the silkworm bioreactor is an ideal production and delivery system for an oral protein vaccine designed to develop immunological tolerance against autoimmune diabetes and CTB functions as an effective mucosal adjuvant for oral tolerance induction.

Induction of Oral Tolerance by Gamma-Irradiated Ovalbumin Administration

  • Yang, Hui;Lee, Junglim;Seo, Ji Hyun;Oh, Kwang Hoon;Cho, Young Ho;Yoo, Yung Choon
    • Food Science of Animal Resources
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    • v.36 no.1
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    • pp.14-18
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    • 2016
  • Oral administration of soluble antigen can induce peripheral tolerance to the antigen. This study was conducted to evaluate whether gamma-irradiated ovalbumin (OVA) can induce oral tolerance. To investigate this, we administrated intact or irradiated OVA to mice, induced allergic response using intact OVA and alum, then compared humoral and cellular immune responses. Mice treated with gammairradiated OVA had less OVA-specific IgE compared with those who were administered intact OVA. There was no difference in levels of OVA-specific IgG+A+M, IgG1, and IgG2a. Splenocytes of mice administered irradiated OVA showed similar OVA-specific T cell proliferation and secretion of IFN-γ and IL-4. However, there was an increase in IL-2 and a decrease of IL-6 secretion in mice treated with irradiated OVA. These results indicate that gamma-irradiated OVA have similar effects to intact OVA on antigen tolerance.

Sex Differences in Pain Threshold and Pain Tolerance and the Effects of Experimenter Gender on Pain Report (남녀별 및 실험자의 성별에 따른 동통역치와 동통내성의 차이)

  • Yun-Kyung Hur;Jae-Kap Choi
    • Journal of Oral Medicine and Pain
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    • v.20 no.1
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    • pp.97-103
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    • 1995
  • The purpose of this study was to evaluate the effect of experimenter gender on pain report as well as the sex differences in pain threshold and pain tolerance. Cold pressor test and pressure pain threshold (PPT) test were performed on forty dental students by both of a male and a female experimenter separately with 1 day interval. The obtained results were as follows : There were no differences in pain threshold and pain tolerance between males and females when they were examined by the same gender experimenter in the cold pressor test, but when they were examined by the opposite gender experimenter the pain threshold of males was significantly higher than females. When the pain threshold was measured by the same gender experimenter, using a algometer, there was no differences in PPT between males and females. However, when the same measurements were done by the opposite gender experimenter, the PPT of males was significantly higher than females at anterior temporalis and inferior masseter. For cold pressor test, females tended to report lower levels of pain threshold and pain tolerance to a male experimenter than a female, but the differences were not significant. Although both pain threshold and pain tolerance were increased when males were examined by a female experimenter in the cold pressor test, the statistical significance was found only in pain tolerance. When subjects were examined by the opposite gender experimenter in the PPT text, females reported significantly higher levels of pain at inferior masseter and males reported significantly lower levels of pain at anterior temporalis and inferior masseter.

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