Chung Y, Chang S Y, Kang C Y
Laboratory of Immunology, College of Pharmacy, Seoul National University, Korea.
J Immunol. 1999 Oct 1;163(7):3692-8.
Oral administration of soluble Ag before immunization induces peripheral tolerance and is effective in suppressing animal models of autoimmune diseases. Although tolerance induction in primed animals is more clinically relevant, it is not well studied. Therefore, this study was designed to examine the feeding effects on different phases of the immune response. We observed that feeding a single high dose (250 mg) of OVA to OVA-primed BALB/c mice could induce OVA-specific suppression in the Ab production and T cell proliferation only at the naive and the activation phases of the immune response, whereas multiple high doses (100 mg/feed for 10 days) were effective at the effector phase. OVA-specific IL-4 production in culture supernatant was also suppressed in the tolerized groups. However, when the mice had resting memory lymphocytes, even multiple feeding regimens were not effective in tolerance induction, although multiple low doses (1 mg/feed for 10 days) partially suppressed Ab production. This phenomenon was confirmed by adoptive transfer study. Nevertheless, the reactivated memory response was suppressed partially by multiple high doses. Our findings have an important implication for understanding the mechanism of oral tolerance and for the therapeutic applications of oral tolerance to autoimmune diseases.
免疫前口服可溶性抗原可诱导外周耐受，并有效抑制自身免疫性疾病的动物模型。虽然在已致敏动物中诱导耐受在临床上更具相关性，但对此研究较少。因此，本研究旨在考察喂食对免疫反应不同阶段的影响。我们观察到，给已用卵清蛋白（OVA）致敏的BALB/c小鼠单次喂食高剂量（250毫克）OVA，仅在免疫反应的初始和激活阶段可诱导OVA特异性抑制抗体产生和T细胞增殖，而多次高剂量（每次100毫克，共喂食10天）在效应阶段有效。耐受组培养上清中OVA特异性白细胞介素-4的产生也受到抑制。然而，当小鼠具有静息记忆淋巴细胞时，即使多次喂食方案也无法有效诱导耐受，尽管多次低剂量（每次1毫克，共喂食10天）可部分抑制抗体产生。过继转移研究证实了这一现象。尽管如此，多次高剂量可部分抑制重新激活的记忆反应。我们的研究结果对于理解口服耐受机制以及口服耐受在自身免疫性疾病治疗中的应用具有重要意义。
