title: Long-term anergy in orally tolerized mice is linked to decreased B7.2 expression on B cells.
abstract: Durable antigen (Ag)-specific T- and B-cell anergy induced by oral tolerance is an attractive strategy for immunotherapy of allergic diseases. Here, we address the lasting effect of oral tolerance induction in naïve or primed mice to ovalbumin (OVA) on antibody production. Single feeding with OVA prior to immunization or double feeding, before and after Ag priming, in A/Sn mice, induced a long-lasting suppression of IgE, IgG1 and IgG2a responses up to 8 months after immunization. In contrast, primed-fed mice had transient IgE inhibition. Naive and double-treated mice showed marked Ag-specific unresponsiveness and scarce cytokines production. Inhibition of IL-2 and IFN-gamma secretion in naïve-fed mice were restored in the presence of anti-CD28 mAb plus Ag stimulation. The durable inhibition of Ab production in OVA-fed mice was related to the persistent decrease of B7.2 expression on B cells. Ag feeding in naive and primed status may be a prophylactic measure to avoid later Ag sensitization.
authors.affiliation: Laboratório de Dermatologia e Imunodeficiências, Faculdade de Medicina da Universidade de São Paulo, Instituto de Medicina Tropical--Prédio II, Av Dr Enéas de Carvalho Aguiar, 500, 3 degrees Andar, 05403-000- São Paulo, Brazil.
authors.forename: Eliana A
authors.initials: EA
authors.lastname: Futata
authors.forename: Cyro A
authors.initials: CA
authors.lastname: de Brito
authors.forename: Jefferson Russo
authors.initials: JR
authors.lastname: Victor
authors.forename: Ana Elisa
authors.initials: AE
authors.lastname: Fusaro
authors.forename: Célia R
authors.initials: CR
authors.lastname: Oliveira
authors.forename: Milton
authors.initials: M
authors.lastname: Maciel
authors.forename: Alberto José
authors.initials: AJ
authors.lastname: da Silva Duarte
authors.forename: Maria Notomi
authors.initials: MN
authors.lastname: Sato
mesh_terms: D000284:Administration, Oral; D000818:Animals; D015703:Antigens, CD / Q000096:biosynthesis / Q000235:genetics; D001402:B-Lymphocytes / Q000276:immunology* / Q000378:metabolism*; D051940:B7-2 Antigen / Q000096:biosynthesis / Q000235:genetics*; D060908:CTLA-4 Antigen; D017635:Clonal Anergy / Q000276:immunology*; D005260:Female; D007132:Immunoglobulin Isotypes / Q000096:biosynthesis / Q000378:metabolism; D007700:Kinetics; D008297:Male; D051379:Mice; D008805:Mice, Inbred A; D010047:Ovalbumin / Q000008:administration & dosage* / Q000276:immunology*; D051381:Rats; D011920:Rats, Inbred WF
chemical_list: D015703:Antigens, CD; D051940:B7-2 Antigen; D060908:CTLA-4 Antigen; C556707:Ctla4 protein, mouse; D007132:Immunoglobulin Isotypes; D010047:Ovalbumin