title: CD4+ T cells anergized by high dose feeding establish oral tolerance to antibody responses when transferred in SCID and nude mice.
abstract: The cellular mechanism for oral tolerance in specific Ab response was investigated by cell-transfer experiments, using severe combined immunodeficiency (SCID) and BALB/c nu/nu mice. High dose feeding with bovine alpha s1-casein, a major allergen in milk, to BALB/c mice induced Ag-specific oral tolerance to the specific Ab response. This state of oral tolerance was successfully transferred to SCID mice with splenocytes from orally tolerant BALB/c mice. In SCID mice that were transferred with tolerant T cells and normal B cells before being immunized with alpha s1-casein, oral tolerance to the Ab responses was generated. In addition, only the T cells established the tolerant state in nude mice. A decreased proliferative response of the splenic T cells from BALB/c mice against alpha s1-casein was also shown, indicating that the decreased Ab responses were attributed to the unresponsiveness of the splenic T cells. Next, the tolerant splenic T cells were further separated into CD4+ T cells and CD8+ T cells, remixed with normal cells, and then transferred to nude mice, which revealed that the tolerant state in the nude mice was principally generated by the CD4+ T cells. When tolerant CD4+ T cells were cotransferred with normal CD4+ T cells to nude mice, there was no significant reduction in the specific Ab responses. These results demonstrate that splenic CD4+ T cells anergized by high dose feeding established oral tolerance to the Ab responses when transferred to SCID and nude mice.
authors.affiliation: Department of Applied Biological Chemistry, University of Tokyo, Japan.
authors.forename: K
authors.initials: K
authors.lastname: Hirahara
authors.forename: T
authors.initials: T
authors.lastname: Hisatsune
authors.forename: K
authors.initials: K
authors.lastname: Nishijima
authors.forename: H
authors.initials: H
authors.lastname: Kato
authors.forename: O
authors.initials: O
authors.lastname: Shiho
authors.forename: S
authors.initials: S
authors.lastname: Kaminogawa
mesh_terms: D000284:Administration, Oral; D000818:Animals; D000917:Antibody Formation; D000941:Antigens / Q000008:administration & dosage; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D002364:Caseins / Q000008:administration & dosage / Q000276:immunology; D002417:Cattle; D005260:Female; D007108:Immune Tolerance; D007116:Immunization, Passive; D066298:In Vitro Techniques; D008213:Lymphocyte Activation; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D016513:Mice, SCID; D013154:Spleen / Q000166:cytology / Q000276:immunology
chemical_list: D000941:Antigens; D002364:Caseins