生分解性ポリマービーヅを用いた経口免疫法の開発と経口免疫寛容の解析への応用

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Oral immunization of antigens has long been recognized as a method to prevent or delay the onset of the diseases associated with untoward immune responses to self and non-self antigens. Although oral administration of antigens offers a convenient way to induce systemictolerance, its therapeutic potential has been seriously limited by the fact that it requires repeated feeding of a large amount of antigens and that it may deteriorate ongoing autoimmune diseases when autoantigens are employed. We have previously shown that orally administered poly-D,L-lactic accid (PDLLA) microspheres containing an antigen were selectively distributed to Peyer's patches (PP) and systemic-lymphoid tissues according to their diameter and then releses the antigen over a long period of time. We reported that a single dose of intragastric imunization with a PDLLA microsphere of appropropriate diameter size containing 2 mg of OVA was as effective as 100 mg of water soluble OVA to suppress OVA-specific IgG ad DTH response. This was associated with a large incresae of IFN-g production by PP T cells stimulated with an antigen and a small increase in secretory IgA specific to OVA. In contrast, administration of an antigen encapsulatead in another appropriate diameter size led to an enhanced OVA-specific IgG response and no significant increase in OVA-specific secretory IgA. Thus, by utilizing microspheres of an appropriate diameter as a vaccination vehicle, we were able to selectively induce both systemic tolerance and sensitization by oral ingestion of single low dose of an antigen.