Selective suppression of antigen-specific Th2 cells by continuous micro-dose oral tolerance

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Abstract
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 α β‐T cell receptor (TCR) genes specific for ovalbumin (OVA) peptide fragment 323 – 339 were continuously fed with micro‐doses of OVA (100 μg/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‐γ 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 suppres sion of the Ag‐specific IgE production, can be achieved by continuous feeding with microdoses of Ag.