The Experts below are selected from a list of 55587 Experts worldwide ranked by ideXlab platform
Barbara L. Kroner - One of the best experts on this subject based on the ideXlab platform.
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Comparison of the International Immune Tolerance Registry and the North American Immune Tolerance Registry
Vox Sanguinis, 1999Co-Authors: Barbara L. KronerAbstract:Two Immune Tolerance registries – the International Immune Tolerance Study Group (ITSG) and North American Immune Tolerance Study (NAITS) – are compared and findings from combined data reported. The r
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Comparison of the international Immune Tolerance registry and the North American Immune Tolerance registry.
Vox sanguinis, 1999Co-Authors: Barbara L. KronerAbstract:Two Immune Tolerance registries--the International Immune Tolerance Study Group (ITSG) and North American Immune Tolerance Study (NAITS) - are compared and findings from combined data reported. The registries differed with respect to data collection tools, location, host and environmental factors, start date distribution and treatment products. The success and failure rates were similar in the two studies. There was a highly significant association between maximum historical titre and Immune Tolerance success; the success rate decreased as the historical titre increased. There was a significant association between inhibitor titre immediately prior to treatment and the probability for treatment success, and between outcome and time from diagnosis to treatment in the ITSG (of borderline significance in the NAITS). There was a significant association between outcome and dose, though the direction of the associations was not the same. In the ITSG, success was associated with doses greater than or equal to 200 IU/kg/day, while in the NAITS, greater success was observed with doses of less than 50 IU/kg/day. There was no association between outcome and treatment product. Data from the two registries were combined to produce a table for calculating the chance of successful treatment by historical titre, pretreatment titre, and dose.
Mübeccel Akdis - One of the best experts on this subject based on the ideXlab platform.
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Influence of Innate Immunity on Immune Tolerance.
Acta medica academica, 2020Co-Authors: Umut C Kucuksezer, Mübeccel Akdis, Cevdet Ozdemir, Cezmi A AkdisAbstract:This review mainly focuses on the mechanisms of peripheral Immune Tolerance within the perspectives of innate immunity. Healthy Immune response requires balanced interaction of the highly specialized elements of immunity within a harmony. Innate immunity supported by microbial pattern recognition receptors, physical anatomical barriers and soluble effectors stands as the first line of defense against non-self-antigens. Innate receptors recognize major classes of pathogens and trigger immediate Immune/inflammatory responses. The decisive action has been the key issue in skewing of Immune reactivity to a pathogen or to tolerate self- and non-self-antigens. Non-responsiveness to self- or to harmless foreign antigens with means of multiple mechanisms is known as Immune Tolerance; a non-inflammatory, non-proliferative and suppressive response linked to suppressor molecules as CTLA-4 and cytokines like IL-10, TGF-β and IL-35, and also to non-inflammatory blocking antibody isotypes as IgG4. Regulatory cells ascertain both induction and maintenance of peripheral Tolerance. Allergic diseases, autoimmunity and transplant rejection are the best illustrations of Immune Tolerance loss. Adaptive immunity responsible for both establishment and maintenance of a long-lasting Immune responsiveness is mainly fine-tuned by actions of innate immunity. Better understanding of the relationship between innate immunity and Immune Tolerance is a prerequisite both for better understanding of pathogenesis of Tolerance-related diseases and also for development of novel therapeutic options. CONCLUSION: Recent evidences point the important roles of innate immunity for establishment of Immune Tolerance with decisive role in central mechanisms. In a peremptory way, a 'balanced Tolerance' is essential for the survival.
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Immune Tolerance in allergy
Current opinion in immunology, 2009Co-Authors: Mübeccel AkdisAbstract:Research on the mechanisms of Immune regulation in allergy and asthma has shown substantial progress in recent years and has led to a variety of allergen-specific therapeutic and preventive approaches. Studies on the area of allergen-specific immunotherapy (allergen-SIT) have provided substantial knowledge on the mechanisms of allergic disease with novel developments for treatment and prevention. Several studies have demonstrated that increased numbers and the activation of allergen-specific T regulatory cells correlate with successful allergen-SIT. Particularly, targeting of the molecular mechanisms of Immune Tolerance and reciprocal regulation of effector and regulatory T-cell subsets are foreseen for the development of new strategies for Immune intervention. This review focuses on current knowledge of Immune Tolerance to allergens in healthy Immune response to allergens and allergen-SIT.
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Therapeutic manipulation of Immune Tolerance in allergic disease
Nature Reviews Drug Discovery, 2009Co-Authors: Mübeccel Akdis, Cezmi A AkdisAbstract:Immune Tolerance — the adaptation of the Immune system to external antigens or allergens — might be therapeutically manipulated to restore normal immunity in conditions such as allergy, asthma and autoImmune diseases. The field of allergen-specific immunotherapy is experiencing exciting and novel developments for the treatment of allergic and autoImmune diseases, and recent insights into the reciprocal regulation and counter-balance between different T-cell subsets is foreseen to facilitate new strategies for immunointervention. This Review highlights current knowledge of immunomodulatory therapies for the manipulation of Immune Tolerance and highlights recent approaches to improve allergen-specific immunotherapy for the treatment of allergic diseases. Immune Tolerance — the adaptation of the Immune system to external antigens or allergens — might be therapeutically manipulated to restore normal immunity in conditions such as allergy, asthma and autoImmune diseases. The physiopathology of Immune-Tolerance-related diseases is complex and is influenced by several factors. T regulatory (T_Reg) cells have become a prime target for strategies aimed at inducing Immune Tolerance. Their pivotal role in maintaining Immune Tolerance was demonstrated in animal models — including allergy, asthmatic lung inflammation, autoImmune diseases and allograft rejection — by restoring Immune Tolerance to allergens, self antigens or alloantigens. In allergen-specific immunotherapy (SIT) peripheral T-cell Tolerance is initiated by the increased autocrine action of allergen-specific T_Reg cells. T_Reg cells directly or indirectly contribute to the control of allergen-specific Immune responses at the level of antigen presentation, T-cell suppression, antibody regulation, suppression of mast cells, basophils and eosinophils, and interaction with resident tissue cells and tissue remodelling in the inflamed lung, nose and skin. Allergen-SIT in humans faces several problems related to the content of the vaccine, type of the adjuvant, route of application, long duration of treatment, side effects and limited efficacy. For this reason intensive research has been carried out to improve efficacy and safety of allergen-SIT during the past several years and many promising studies have been completed. There is a substantial focus on the development of immunomodulatory drugs for allergy and asthma. Some of these could be combined with allergen-SIT to improve their efficacy and safety. Immune Tolerance might be therapeutically manipulated to restore normal immunity in allergic disease. This Review highlights current knowledge of immunomodulatory therapies for the manipulation of Immune Tolerance and discusses recent approaches to improve allergen-specific immunotherapy.
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Therapeutic manipulation of Immune Tolerance in allergic disease
Nature Reviews Drug Discovery, 2009Co-Authors: Mübeccel Akdis, Cezmi A AkdisAbstract:Immune Tolerance - the adaptation of the Immune system to external antigens or allergens - might be therapeutically manipulated to restore normal immunity in conditions such as allergy, asthma and autoImmune diseases. The field of allergen-specific immunotherapy is experiencing exciting and novel developments for the treatment of allergic and autoImmune diseases, and recent insights into the reciprocal regulation and counter-balance between different T-cell subsets is foreseen to facilitate new strategies for immunointervention. This Review highlights current knowledge of immunomodulatory therapies for the manipulation of Immune Tolerance and highlights recent approaches to improve allergen-specific immunotherapy for the treatment of allergic diseases.
Cezmi A Akdis - One of the best experts on this subject based on the ideXlab platform.
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Influence of Innate Immunity on Immune Tolerance.
Acta medica academica, 2020Co-Authors: Umut C Kucuksezer, Mübeccel Akdis, Cevdet Ozdemir, Cezmi A AkdisAbstract:This review mainly focuses on the mechanisms of peripheral Immune Tolerance within the perspectives of innate immunity. Healthy Immune response requires balanced interaction of the highly specialized elements of immunity within a harmony. Innate immunity supported by microbial pattern recognition receptors, physical anatomical barriers and soluble effectors stands as the first line of defense against non-self-antigens. Innate receptors recognize major classes of pathogens and trigger immediate Immune/inflammatory responses. The decisive action has been the key issue in skewing of Immune reactivity to a pathogen or to tolerate self- and non-self-antigens. Non-responsiveness to self- or to harmless foreign antigens with means of multiple mechanisms is known as Immune Tolerance; a non-inflammatory, non-proliferative and suppressive response linked to suppressor molecules as CTLA-4 and cytokines like IL-10, TGF-β and IL-35, and also to non-inflammatory blocking antibody isotypes as IgG4. Regulatory cells ascertain both induction and maintenance of peripheral Tolerance. Allergic diseases, autoimmunity and transplant rejection are the best illustrations of Immune Tolerance loss. Adaptive immunity responsible for both establishment and maintenance of a long-lasting Immune responsiveness is mainly fine-tuned by actions of innate immunity. Better understanding of the relationship between innate immunity and Immune Tolerance is a prerequisite both for better understanding of pathogenesis of Tolerance-related diseases and also for development of novel therapeutic options. CONCLUSION: Recent evidences point the important roles of innate immunity for establishment of Immune Tolerance with decisive role in central mechanisms. In a peremptory way, a 'balanced Tolerance' is essential for the survival.
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Therapeutic manipulation of Immune Tolerance in allergic disease
Nature Reviews Drug Discovery, 2009Co-Authors: Mübeccel Akdis, Cezmi A AkdisAbstract:Immune Tolerance — the adaptation of the Immune system to external antigens or allergens — might be therapeutically manipulated to restore normal immunity in conditions such as allergy, asthma and autoImmune diseases. The field of allergen-specific immunotherapy is experiencing exciting and novel developments for the treatment of allergic and autoImmune diseases, and recent insights into the reciprocal regulation and counter-balance between different T-cell subsets is foreseen to facilitate new strategies for immunointervention. This Review highlights current knowledge of immunomodulatory therapies for the manipulation of Immune Tolerance and highlights recent approaches to improve allergen-specific immunotherapy for the treatment of allergic diseases. Immune Tolerance — the adaptation of the Immune system to external antigens or allergens — might be therapeutically manipulated to restore normal immunity in conditions such as allergy, asthma and autoImmune diseases. The physiopathology of Immune-Tolerance-related diseases is complex and is influenced by several factors. T regulatory (T_Reg) cells have become a prime target for strategies aimed at inducing Immune Tolerance. Their pivotal role in maintaining Immune Tolerance was demonstrated in animal models — including allergy, asthmatic lung inflammation, autoImmune diseases and allograft rejection — by restoring Immune Tolerance to allergens, self antigens or alloantigens. In allergen-specific immunotherapy (SIT) peripheral T-cell Tolerance is initiated by the increased autocrine action of allergen-specific T_Reg cells. T_Reg cells directly or indirectly contribute to the control of allergen-specific Immune responses at the level of antigen presentation, T-cell suppression, antibody regulation, suppression of mast cells, basophils and eosinophils, and interaction with resident tissue cells and tissue remodelling in the inflamed lung, nose and skin. Allergen-SIT in humans faces several problems related to the content of the vaccine, type of the adjuvant, route of application, long duration of treatment, side effects and limited efficacy. For this reason intensive research has been carried out to improve efficacy and safety of allergen-SIT during the past several years and many promising studies have been completed. There is a substantial focus on the development of immunomodulatory drugs for allergy and asthma. Some of these could be combined with allergen-SIT to improve their efficacy and safety. Immune Tolerance might be therapeutically manipulated to restore normal immunity in allergic disease. This Review highlights current knowledge of immunomodulatory therapies for the manipulation of Immune Tolerance and discusses recent approaches to improve allergen-specific immunotherapy.
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Therapeutic manipulation of Immune Tolerance in allergic disease
Nature Reviews Drug Discovery, 2009Co-Authors: Mübeccel Akdis, Cezmi A AkdisAbstract:Immune Tolerance - the adaptation of the Immune system to external antigens or allergens - might be therapeutically manipulated to restore normal immunity in conditions such as allergy, asthma and autoImmune diseases. The field of allergen-specific immunotherapy is experiencing exciting and novel developments for the treatment of allergic and autoImmune diseases, and recent insights into the reciprocal regulation and counter-balance between different T-cell subsets is foreseen to facilitate new strategies for immunointervention. This Review highlights current knowledge of immunomodulatory therapies for the manipulation of Immune Tolerance and highlights recent approaches to improve allergen-specific immunotherapy for the treatment of allergic diseases.
Wanjun Chen - One of the best experts on this subject based on the ideXlab platform.
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Apoptotic cell-linked immunoregulation: implications for promoting Immune Tolerance in transplantation
Cell & bioscience, 2015Co-Authors: Ruixia Kuang, Sylvain Perruche, Wanjun ChenAbstract:The induction of alloantigen-specific Immune Tolerance is the “Holy-Grail” in transplantation. Although it had been previously demonstrated that transient depletion of T cells through apoptosis could lead to long-term Immune Tolerance, the underlying mechanism responsible for this Tolerance induction and maintenance was unknown. In this short article, a novel mechanism for long-term Immune Tolerance via transient T cell apoptosis will be discussed, based on our recent findings in a CD3-specific antibody treatment-induced Immune Tolerance mouse model. Transforming growth factor-β, which is produced by immature dendritic cells whilst they phagocytose apoptotic T cells and by macrophages, plays an important role in initiating long-term Immune Tolerance. A possible model of how allospecific-Immune Tolerance can be induced in order to prevent allograft rejection in transplantation will be also proposed.
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CD3-specific antibody-induced Immune Tolerance involves transforming growth factor-beta from phagocytes digesting apoptotic T cells.
Nature Medicine, 2008Co-Authors: Sylvain Perruche, Pin Zhang, Yongzhong Liu, Philippe Saas, Jeffrey Bluestone, Wanjun ChenAbstract:Intact CD3-specific antibody transiently depletes large numbers of T cells and subsequently induces long-term Immune Tolerance. The underlying mechanisms for the systemic Tolerance, however, remain unclear. We show here that treatment of normal mice with intact antibody to CD3 increases systemic transforming growth factor-beta (TGF-beta) produced by phagocytes exposed to apoptotic T cells. Among the phagocytes, macrophages and immature dendritic cells (iDCs) secrete TGF-beta upon ingestion of apoptotic T cells, which induces CD4+Foxp3+ regulatory T cells in culture and contributes to Immune Tolerance mediated by CD3-specific antibody in vivo. In accordance with these results, depletion of macrophages and iDCs not only abrogates CD3-specific antibody-mediated prevention of myelin oligodendrocyte glycoprotein-induced acute experimental autoImmune encephalomyelitis (EAE), but also reverses the therapeutic effects of antibody to CD3 on established disease in a model of relapsing-remitting EAE. Thus, CD3-specific antibody-induced Immune Tolerance is associated with TGF-beta production in phagocytes involved in clearing apoptotic T cells, which suggests that apoptosis is linked to active suppression in Immune Tolerance.
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cd3 specific antibody induced Immune Tolerance involves transforming growth factor β from phagocytes digesting apoptotic t cells
Nature Medicine, 2008Co-Authors: Sylvain Perruche, Jeffrey A. Bluestone, Pin Zhang, Yongzhong Liu, Philippe Saas, Wanjun ChenAbstract:Intact CD3-specific antibody transiently depletes large numbers of T cells and subsequently induces long-term Immune Tolerance. The underlying mechanisms for the systemic Tolerance, however, remain unclear. We show here that treatment of normal mice with intact antibody to CD3 increases systemic transforming growth factor-β (TGF-β) produced by phagocytes exposed to apoptotic T cells. Among the phagocytes, macrophages and immature dendritic cells (iDCs) secrete TGF-β upon ingestion of apoptotic T cells, which induces CD4+Foxp3+ regulatory T cells in culture and contributes to Immune Tolerance mediated by CD3-specific antibody in vivo. In accordance with these results, depletion of macrophages and iDCs not only abrogates CD3-specific antibody–mediated prevention of myelin oligodendrocyte glycoprotein–induced acute experimental autoImmune encephalomyelitis (EAE), but also reverses the therapeutic effects of antibody to CD3 on established disease in a model of relapsing-remitting EAE. Thus, CD3-specific antibody–induced Immune Tolerance is associated with TGF-β production in phagocytes involved in clearing apoptotic T cells, which suggests that apoptosis is linked to active suppression in Immune Tolerance.
Hossam M Ashour - One of the best experts on this subject based on the ideXlab platform.
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Immune Tolerance elicited via unique ocular and oral routes.
Current molecular medicine, 2015Co-Authors: Hossam M AshourAbstract:Immune Tolerance can be induced by numerous methods. This review article aims to draw lines of similarity and contrast between two unique models of Immune Tolerance, namely Anterior Chamber Associated Immune Deviation (ACAID) and Nickel-induced oral Tolerance. ACAID is an Immune Tolerance model that leads to the generation of CD4(+) T regulatory cells and CD8(+) T regulatory cells in the periphery after the injection of an antigen into the anterior chamber of the eye. Nickel-induced oral Tolerance is another Immune Tolerance model that is induced by the contact allergen Nickel and leads to the generation of Nickel-specific CD4(+) CD25(+) T regulatory cells after oral exposure. The goal of comparing different models of Immune Tolerance is to identify which mechanisms are universal and which mechanisms are model-specific. The knowledge of such mechanisms would allow scientists and clinicians to better intervene in different Immune deregulation scenarios.
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Eye-mediated Immune Tolerance to Type II collagen in arthritis-prone strains of mice.
Journal of cellular and molecular medicine, 2014Co-Authors: Shukkur M. Farooq, Ashok Kumar, Hossam M AshourAbstract:Type II collagen (CII) is a cartilage structural protein that plays important roles in joint function, arthritis and ageing. In studying the ability of CII to induce eye-mediated specific Immune Tolerance, we have recently proven that CII is capable of inducing anterior chamber-associated Immune deviation (ACAID) in Balb/c mice. Here, we study the ability of CII to induce eye-mediated Immune Tolerance in strains of mice that are prone to the induction of rheumatoid arthritis. Thus, we hypothesized that CII induces ACAID in DBA/1 mice and in C57BL/6 mice through the AC route (direct injection) or the intravenous route (adoptive transfer of in vitro-generated CII-specific ACAID macrophages or of CII-specific in vitro-generated T regulatory cells). Specific Immune Tolerance induction was assessed using both delayed-type hypersensitivity (DTH) and local adoptive transfer (LAT) assays. Results indicated the ability of CII to generate CII-specific ACAID-mediated Immune Tolerance in vivo and in vitro in both DBA/1 mice and C57BL/6 mice. These findings could be beneficial in studies of Immune Tolerance induction using CII.
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Eye-mediated induction of specific Immune Tolerance to encephalitogenic antigens.
CNS neuroscience & therapeutics, 2013Co-Authors: Shukkur M. Farooq, Hossam M AshourAbstract:Summary Aims Administration of antigens into the anterior chamber (AC) of the eye induces a form of antigen-specific Immune Tolerance termed anterior chamber-associated Immune deviation (ACAID). This Immune Tolerance effectively impairs host delayed-type hypersensitivity (DTH) responses. We hypothesized that ACAID could be generated in BALB/c mice following AC inoculation of the encephalitogenic antigens myelin oligodendrocyte glycoprotein (MOG) and myelin basic protein (MBP). Methods We used DTH assays and local adoptive transfer (LAT) assays to test whether MOG/MBP-induced ACAID following their administration into the AC, whether they elicited this Immune Tolerance via CD8+ T cells, and whether their AC coadministration (MOG/MBP) induced specific Immune Tolerance to one or both antigens. Results We showed that MOG/MBP-induced AC-mediated specific Immune Tolerance, as evident from impaired DTH responses. This antigen-driven DTH suppression was solely mediated via splenic CD8+ T cells as confirmed by LAT assays. Finally, a single AC injection with both antigens was sufficient to induce specific Immune Tolerance to these antigens, as evident from DTH and LAT assays. Conclusion ACAID T-cell regulation could be used as a therapeutic tool in the treatment of complicated autoImmune diseases that involve multiple antigens such as multiple sclerosis.
