title: Priming or tolerization of the B- and Th2-dependent immune response by the oral administration of OVA-DNP is determined by the antigen dosage.
abstract: In the present report we established antigen dosages that induce oral tolerance of Th1 and Th2 lymphocytes or instead prime B- and Th2-dependent immune response and induce the tolerance of Th1 lymphocytes. Using different hapten-carrier systems, we found that low doses of OVA-DNP administered orally primed B and Th2 cells. On the other hand, no priming of B or Th2 cells was found in high-dose-OVA-DNP-fed rats. Low-dose-OVA-DNP-fed rats showed a strong mucosal immune response, with a high number of IgA anti-DNP antibody-forming cells in the lamina propria, while no mucosal immune response was observed in high-dose-OVA-DNP-fed rats. Thirty days after the immunization, tolerization of Th1 lymphocytes was confirmed in low- and high-dose-OVA-DNP-fed rats by diminished antigen-specific proliferation in vitro, reduced titers of anti-DNP IgG2a in serum, reduced expression of CD25 and CD134 molecules in cultured cells exposed to the antigen, reduced DTH reaction, and reduced IL-2 synthesis in culture. On the other hand, a high dose of OVA-DNP led to Th1 and Th2 tolerance, with an inhibition of specific IgG1 and IgG2a anti-DNP antibodies in serum after a parenteral challenge with OVA in CFA. This functional evidence was supported by the direct examination of IL-2 and IL-4 production. Furthermore, whereas in vitro assays seem to indicate that active suppression could be the responsible for Th1 tolerization in low-dose-OVA-DNP-fed rats, the results obtained after the transference of spleen or MLN cells to naive recipients support the idea that a subtractive mechanism is behind the tolerization of Th1 lymphocytes.
authors.affiliation: Faculty of Exact and Natural Sciences, University of Buenos Aires, Buenos Aires, Argentina.
authors.forename: L
authors.initials: L
authors.lastname: Franco
authors.forename: R
authors.initials: R
authors.lastname: Benedetti
authors.forename: G A
authors.initials: GA
authors.lastname: Ferek
authors.forename: E
authors.initials: E
authors.lastname: Massouh
authors.forename: J
authors.initials: J
authors.lastname: Fló
mesh_terms: D000284:Administration, Oral; D019264:Adoptive Transfer; D000818:Animals; D000917:Antibody Formation; D000941:Antigens / Q000008:administration & dosage*; D001402:B-Lymphocytes / Q000276:immunology*; D016207:Cytokines / Q000096:biosynthesis; D004140:Dinitrophenols / Q000008:administration & dosage* / Q000276:immunology*; D004306:Dose-Response Relationship, Immunologic; D005260:Female; D007108:Immune Tolerance; D018928:Immunity, Mucosal; D066298:In Vitro Techniques; D008198:Lymph Nodes / Q000166:cytology / Q000276:immunology; D008213:Lymphocyte Activation; D010047:Ovalbumin / Q000008:administration & dosage* / Q000276:immunology*; D051381:Rats; D017208:Rats, Wistar; D013154:Spleen / Q000166:cytology / Q000276:immunology; D018417:Th1 Cells / Q000276:immunology; D018418:Th2 Cells / Q000276:immunology*
chemical_list: D000941:Antigens; D016207:Cytokines; D004140:Dinitrophenols; C045521:dinitrophenol-ovalbumin; D010047:Ovalbumin