Selective suppression of antigen-specific Th2 cells by continuous micro-dose oral tolerance.
The effect on antigen (Ag)-specific Th2 response as well as IgE production of continuous oral administration of micro-doses of Ag was investigated. Transgenic (Tg) mice carrying the alphabeta-T cell receptor (TCR) genes specific for ovalbumin (OVA) peptide fragment 323-339 were continuously fed with micro-doses of OVA (100 microg/day) for 14 days. Mice were first immunized by OVA in alum and pertussis toxin 7 days before the oral feeding and given a second immunization 1 day after the oral treatment. This feeding regimen tolerized Th2 but not Th1 responses as shown by decrease of Ag-driven cell proliferation and cytokine secretion of IL-4 but not of IL-2 or IFN-gamma as well as by the absence of Ag-specific antibody production of IgE and IgG1, but not of IgG2a or total IgG. Numbers of clonotype-specific TCR-high CD4-positive T cells in peripheral lymphoid tissues markedly decreased in the orally treated group but not in the control group. However, total numbers of CD4-positive T cells in thymus, spleen and lymph nodes were not affected by the oral treatment, indicating that tolerance induction in Th2 cells was mainly due to the down-regulation of TCR and not clonal deletion. The population of antigen-presenting cells expressing B7-2 (CD86) Ag on the surface was decreased in the spleen of the mice which underwent the feeding regimen. The present results suggest that Ag-specific low responsiveness in Th2 cells, which resulted in suppression of the Ag-specific IgE production, can be achieved by continuous feeding with microdoses of Ag.
Wu
X M
XM
Department of Molecular Immunology, Medical Institute of Bioregulation, Kyushu University, Fukuoka, Japan.
Nakashima
M
M
Watanabe
T
T
D000284:Administration, Oral; D000818:Animals; D000917:Antibody Formation; D000918:Antibody Specificity; D003888:Desensitization, Immunologic / Q000379:methods*; D004306:Dose-Response Relationship, Immunologic; D007114:Immunization / Q000379:methods; D007115:Immunization Schedule; D007117:Immunization, Secondary; D007073:Immunoglobulin E / Q000096:biosynthesis; D007165:Immunosuppression Therapy / Q000379:methods*; D008211:Lymphocyte Cooperation; D008221:Lymphoid Tissue / Q000276:immunology; D008222:Lymphokines / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D008822:Mice, Transgenic; D010047:Ovalbumin / Q000008:administration & dosage* / Q000276:immunology; D010446:Peptide Fragments / Q000008:administration & dosage* / Q000276:immunology; D037342:Pertussis Toxin; D018417:Th1 Cells / Q000276:immunology; D018418:Th2 Cells / Q000276:immunology*; D010566:Virulence Factors, Bordetella / Q000276:immunology
D008222:Lymphokines; D010446:Peptide Fragments; D010566:Virulence Factors, Bordetella; D007073:Immunoglobulin E; D010047:Ovalbumin; D037342:Pertussis Toxin