Mechanism underlying polyvalent IgG-induced regulatory T cell activation and its clinical application: Anti-idiotypic regulatory T cell theory for immune tolerance

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dc.contributorSistema FMUSP-HC: Faculdade de Medicina da Universidade de São Paulo (FMUSP) e Hospital das Clínicas da FMUSP
dc.contributor.authorVICTOR, Jefferson Russo
dc.contributor.authorNAHM, Dong-Ho
dc.date.accessioned2024-02-15T14:55:22Z
dc.date.available2024-02-15T14:55:22Z
dc.date.issued2023
dc.description.abstractThe regulatory T (Treg) cells constitute a functionally defined subpopulation of T cells that modulate the immune system and maintain immune tolerance through suppression of the development of autoimmune responses to self-antigens and allergic reactions to external antigens. Reduction in the number or function of Treg cells has been suggested as a key immune abnormality underlying the development of autoimmune and allergic diseases. In vitro studies have demonstrated that purified polyvalent immunoglobulin G (IgG) from multiple healthy blood donors can exert immunomodulatory effects on Treg cells. Incubation of polyvalent human IgG with purified CD4+CD25high T cells increased the intracellular expression of interleukin (IL)-10. Intravenous administration of polyvalent human IgG induced significant expansions of CD4+ Foxp3+ Treg cells and clinical improvements in patients with autoimmune diseases. In human clinical trials, intramuscular administration of autologous total IgG significantly increased the percentage of IL-10-producing CD4+ Treg cells in the peripheral blood of healthy subjects and provided significant clinical improvements in patients with atopic dermatitis. These results suggest a clinical usefulness of polyvalent IgG-induced activation of Treg cells in human subjects. This review proposes a new hypothesis for immune tolerance mechanism by integrating the pre-existing ""idiotypic network theory"" and ""Treg cell theory"" into an ""anti-idiotypic Treg cell theory."" Based on this hypothesis, an ""active anti-idiotypic therapy"" for allergic and autoimmune diseases using autologous polyvalent IgG (as immunizing antigens) is suggested as follows: (1) Intramuscular or subcutaneous administration of autologous polyvalent IgG produces numerous immunogenic peptides derived from idiotypes of autologous IgG through processing of dendritic cells, and these peptides activate anti-idiotypic Treg cells in the same subject. (2) Activated anti-idiotypic Treg cells secrete IL-10 and suppress Th2 cell response to allergens and autoimmune T cell response to self-antigens. (3) These events can induce a long-term clinical improvements in patients with allergic and autoimmune diseases. Further studies are needed to evaluate the detailed molecular mechanism underlying polyvalent IgG-induced Treg cell activation and the clinical usefulness of this immunomodulatory therapy for autoimmune and allergic diseases.eng
dc.description.indexMEDLINE
dc.description.indexPubMed
dc.description.indexWoS
dc.description.indexScopus
dc.description.sponsorshipNational Research Foundation of Korea10.13039/501100003725
dc.identifier.citationFRONTIERS IN IMMUNOLOGY, v.14, article ID 1242860, 14p, 2023
dc.identifier.doi10.3389/fimmu.2023.1242860
dc.identifier.issn1664-3224
dc.identifier.urihttps://observatorio.fm.usp.br/handle/OPI/58148
dc.language.isoeng
dc.publisherFRONTIERS MEDIA SAeng
dc.relation.ispartofFrontiers in Immunology
dc.rightsopenAccesseng
dc.rights.holderCopyright FRONTIERS MEDIA SAeng
dc.subjectimmunoglobulinseng
dc.subjectT-lymphocyteseng
dc.subjectimmunomodulationeng
dc.subjectregulatory T celleng
dc.subjectatopic dermatitiseng
dc.subjectimmune toleranceeng
dc.subjectallergic diseaseeng
dc.subjectautoimmune diseaseeng
dc.subject.otherallergen-specific immunotherapyeng
dc.subject.othersevere atopic-dermatitiseng
dc.subject.othertotal immunoglobulin-geng
dc.subject.otherintravenous immunoglobulineng
dc.subject.otherautologous immunoglobulineng
dc.subject.otherreciprocal regulationeng
dc.subject.otherantigen presentationeng
dc.subject.otherautoimmuneeng
dc.subject.otherfceng
dc.subject.othertherapyeng
dc.subject.wosImmunologyeng
dc.titleMechanism underlying polyvalent IgG-induced regulatory T cell activation and its clinical application: Anti-idiotypic regulatory T cell theory for immune toleranceeng
dc.typearticleeng
dc.type.categoryrevieweng
dc.type.versionpublishedVersioneng
dspace.entity.typePublication
hcfmusp.affiliation.countryCoréia do Sul
hcfmusp.affiliation.countryisokr
hcfmusp.author.externalNAHM, Dong-Ho:Ajou Univ, Sch Med, Dept Allergy & Clin Immunol, Suwon, South Korea
hcfmusp.citation.scopus2
hcfmusp.contributor.author-fmusphcJEFFERSON RUSSO VICTOR
hcfmusp.description.articlenumber1242860
hcfmusp.description.volume14
hcfmusp.origemWOS
hcfmusp.origem.pubmed38094290
hcfmusp.origem.scopus2-s2.0-85179338263
hcfmusp.origem.wosWOS:001122677600001
hcfmusp.publisher.cityLAUSANNEeng
hcfmusp.publisher.countrySWITZERLANDeng
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