• 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.

• Journal of the Institute of Electronics Engineers of Korea CI
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• v.41 no.4
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• pp.51-58
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• 2004

This paper proposes a new artificial immune approach to on-line hardware test which is the most indispensable technique for fault tolerant hardware. A novel algorithm of generating tolerance conditions is suggested based on the principle of the antibody diversity. Tolerance conditions in artificial immune system correspond to the antibody in biological immune system. In addition, antigen presenting cell (APC) is realized by Quine-McCluskey method in this algorithm and tolerance conditions are generated through GA (Genetic Algorithm). The suggested method is applied to the on-line monitoring of a typical FSM (a decade counter) and its effectiveness is demonstrated by the computer simulation.

• Clinical and Experimental Pediatrics
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• v.56 no.12
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• pp.505-513
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• 2013

Because the prevalence of allergic diseases has significantly increased in recent years, understanding the causes and mechanisms of these disorders is of high importance, and intense investigations are ongoing. Current knowledge pinpoints immune tolerance mechanisms as indispensable for healthy immune response to allergens in daily life. It is evident that development and maintenance of allergen-specific T cell tolerance is of vital importance for a healthy immune response to allergens. Such tolerance can be gained spontaneously by dose-dependent exposures to allergens in nature or by allergen-specific immunotherapy. Allergen-specific immunotherapy induces regulatory T cells with the capacity to secrete interleukin-10 and transforming growth factor-${\beta}$, limits activation of effector cells of allergic inflammation (such as mast cells and basophils), and switches antibody isotype from IgE to the noninflammatory type IgG4. Although allergen-specific immunotherapy is the only method of tolerance induction in allergic individuals, several factors, such as long duration of treatment, compliance problems, and life-threatening side effects, have limited widespread applicability of this immunomodulatory treatment. To overcome these limitations, current research focuses on the introduction of allergens in more efficient and safer ways. Defining the endotypes and phenotypes of allergic diseases might provide the ability to select ideal patients, and novel biomarkers might ensure new custom-tailored therapy modalities.

• Clinical and Experimental Pediatrics
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• v.50 no.12
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• pp.1165-1172
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• 2007

Self/non-self discrimination and unresponsiveness to self is the fundamental properties of the immune system. Self-tolerance is a state in which the individual is incapable of developing an immune response to an individual's own antigens and it underlies the ability to remain tolerant of individual's own tissue components. Several mechanisms have been postulated to explain the tolerant state. They can be broadly classified into two groups: central tolerance and peripheral tolerance. Several mechanisms exist, some of which are shared between T cells and B cells. In central tolerance, the recognition of self-antigen by lymphocytes in bone marrow or thymus during development is required, resulting in receptor editing (revision), clonal deletion, anergy or generation of regulatory T cells. Not all self-reactive B or T cells are centrally purged from the repertoire. Additional mechanisms of peripheral tolerance are required, such as anergy, suppression, deletion or clonal ignorance. Tolerance is antigen specific. Generating and maintaining the self-tolerance for T cells and B cells are complex. Failure of self-tolerance results in immune responses against self-antigens. Such reactions are called autoimmunity and may give rise to autoimmune diseases. Development of autoimmune disease is affected by properties of the genes of the individual and the environment, both infectious and non-infectious. The host's genes affect its susceptibility to autoimmunity and the environmental factors promote the activation of self-reactive lymphocytes, developing the autoimmunity. The changes in participating antigens (epitope spreading), cells, cytokines or other inflammatory mediators contribute to the progress from initial activation to a chronic state of autoimmune diseases.

• International Journal of Fuzzy Logic and Intelligent Systems
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• v.3 no.1
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• pp.23-26
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• 2003

This paper proposes a new artificial immune approach to hardware test. A novel algorithm of generating tolerance conditions is suggested based on the principle of the antibody diversity. Tolerance conditions in artificial immune system correspond to the antibody in biological immune system. The suggested method is applied to the on-line monitoring of a typical FSM (a decade counter) and its effectiveness is demonstrated by the computer simulation.

• Proceedings of the IEEK Conference
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• 2003.07c
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• pp.2673-2676
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• 2003

This Paper proposes a new artificial immune approach to hardware test. A Novel Algorithm of generating tolerance conditions is suggested based on the principle of the antibody diversity. Tolerance conditions in artificial immune system correspond to the antibody in biological immune system. The suggested method is applied to the on-line monitoring of a typical FSM (a decade counter) and its effectiveness is demonstrated by the computer simulation.

• 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.

• 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.

• IMMUNE NETWORK
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• v.16 no.1
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• pp.44-51
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• 2016

Dendritic cells (DCs) are professional antigen presenting cells, and play an important role in the induction of antigen-specific adaptive immunity. However, some DC populations are involved in immune regulation and immune tolerance. These DC populations are believed to take part in the control of immune exaggeration and immune disorder, and maintain immune homeostasis in the body. Tolerogenic DCs (tolDCs) can be generated in vitro by genetic or pharmacological modification or by controlling the maturation stages of cytokine-derived DCs. These tolDCs have been investigated for the treatment of rheumatoid arthritis (RA) in experimental animal models. In the last decade, several in vitro and in vivo approaches have been translated into clinical trials. As of 2015, three tolDC trials for RA are on the list of ClinicalTrial.gov (www.clinicaltrials.gov). Other trials for RA are in progress and will be listed soon. In this review, we discuss the evolution of tolDC-based immunotherapy for RA and its limitations and future prospects.

• IMMUNE NETWORK
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• v.11 no.6
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• pp.358-363
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• 2011

Background: Traditionally, interferon-${\gamma}$ (IFN-${\gamma}$) was regarded as a pro-inflammatory cytokine, however, recent reports suggested role of IFN-${\gamma}$ in immune tolerance. In our previous report, we could induce tolerance to male antigen (HY) just by male islet transplantation in wild type C57BL/6 mice without any immunological intervention. We tried to investigate the influence of IFN-${\gamma}$ deficiency on tolerance induction by male islet transplantation. Methods: To examine the immunogenicity of male tissue in the absence of IFN-${\gamma}$, we transplanted male IFN-${\gamma}$ knock-out (KO) skin to female IFN-${\gamma}$ KO mice. Next, we analyzed male IFN-${\gamma}$ KO islet to streptozotocin-induced diabetic female IFN-${\gamma}$ KO mice. And, we checked the functionality of grafted islet by graft removal and insulin staining. Results: As our previous results in wild type C57BL/6 mice, female IFN-${\gamma}$ KO mice rejected male IFN-${\gamma}$ KO skin within 29 days, and did not reject male IFN-${\gamma}$ KO islet. The maintenance of normal blood glucose level was dependent on the presence of grafted male islet. And the male islet recipient did not reject 2nd challenge of male islet graft also. Conclusion: Deficiency of IFN-${\gamma}$ does not have influence on the result of male skin graft and male islet transplantation. Conclusively, male islet transplantation induced T cell tolerance is not dependent on the presence of IFN-${\gamma}$.