SUMMARYOne of the main goals of immunotherapy of allergic diseases is the down-regulation of the type I hypersensitivity reaction. We investigated in this study the effect of oral administration of varying doses (0·25, 1·0, 4·0 and 10 mg) of dust mite extract (Dermatophagoides pteronyssinus, Dp) in sensitized A/Sn mice. A marked decrease of the allergen-specific immunoglobulin E (IgE) response was observed with all antigen doses. The mice orally tolerized with low Dp dose (0·25 mg) had a significant decrease in the total serum IgE and in the immunoglobulin G1 (IgG1), IgG2a and IgG2b antibody levels. The higher Dp dose (10·0 mg), however, enhanced the IgG1 antibody response, suggesting the stimulation of a pre-existing immune response of the sensitized animals. Animals fed with the low Dp dose had a significant decrease in the frequency of interleukin-4 (IL-4) secreting cells. These animals also showed a significant decrease in the frequency of Dp-specific IgE-and IgG1-positive plasma cells. Our data suggest that feeding dust mite extract to Dp-sensitized mice down-regulates the development of type I hypersensitivity, by inhibition of the T helper 2 response. INTRODUCTIONit is unclear how and whether these oral tolerance-induced IL-4-producing cells can modulate allergic responses that are In allergic processes, cytokines secreted by T helper 2 (Th2) themselves mediated by Th2 cells. cells, such as interleukin-4 (IL-4), play a pivotal role on the Oral tolerance protocol is usually studied in naive animals.1 onset and maintenance of immunoglobulin E (IgE) responses.The evaluation in previously immunized animals is of parThis observation is the rationale for treatments of allergic ticular interest to the development of immunotherapeutic response that are based on the down-regulation of Th2 cell approaches for human allergic diseases. However, these studies functions.must take into account that oral administration of antigen to One of the protocols used to induce antigen-specific sysimmunized animals might occasionally enhance a pre-existing temic immune tolerance is based on the oral antigen adminisimmune response.11-13 We have previously shown that the oral tration followed by a challenge with the same antigen.1 administration of Dp has a more pronounced inhibitory effect Suppression of Th1-mediated inflammatory responses by oral in sensitized mice than in naive mice.14 The induction of oral administration of autoantigen has been observed in several tolerance is a complex process that is influenced by many autoimmune disease and transplantation models.2,3 Among factors, such as animal age, genetic background and dose and the oral tolerance applications, there is a special interest in the administration regimen of the tolerogen.15 modulation of the Th2-allergic-mediated diseases,4-7 since Th1In the present work, we investigated the effect of oral and Th2 cells can be inactivated by feeding antigen.8 administration of varying doses of dust mite extract in a CD4 lymphocytes have an important role on the regulation mu...