Mowat A M
Immunology. 1985 Oct;56(2):253-60.
The induction of tolerance by feeding proteins may prevent potentially harmful delayed-type hypersensitivity (DTH) reactions to food antigens. Suppressor T cells (Ts) are present in mice with tolerance of systemic DTH after feeding ovalbumin (OVA) but, as other immunoregulatory mechanisms have also been described, the exact role of Ts in maintaining tolerance is not known. In this study, we have used the ability of native and denaturated OVA to cross-react at the level of helper/effector T cells, but not Ts, to re-examine the role of Ts in oral tolerance to OVA. Mice immunized with native OVA (nOVA) or denatured OVA (dOVA) in adjuvant had fully cross-reacting DTH to either nOVA or dOVA, but intravenous administration of antigen induced Ts which were specific for the appropriate form. Mice fed nOVA or dOVA had identical tolerance of systemic DTH to both forms of OVA, and feeding nOVA induced splenic Ts which suppressed the DTH response to both nOVA and dOVA. Splenic Ts could not be detected in mice fed dOVA. The results support the hypothesis that tolerance of systemic DTH in mice fed native proteins is due to Ts. Although, for the moment, there is no complementary evidence for a role for Ts in oral tolerance to denatured proteins, this study is consistent with the idea that Ts are the mechanism which normally prevent enteropathy due to DTH against dietary proteins. In addition, our study underlines the differences between orally and parenterally induced Ts and reinforces the view that fed proteins induce Ts after processing by the gut or its lymphoid accessory cells.
通过喂食蛋白质诱导耐受性可能会预防对食物抗原潜在有害的迟发型超敏反应(DTH)。喂食卵清蛋白(OVA)后,具有全身性DTH耐受性的小鼠体内存在抑制性T细胞(Ts),但由于也描述了其他免疫调节机制,Ts在维持耐受性中的确切作用尚不清楚。在本研究中,我们利用天然和变性OVA在辅助/效应T细胞水平而非Ts水平交叉反应的能力,重新审视Ts在OVA口服耐受性中的作用。用佐剂中的天然OVA(nOVA)或变性OVA(dOVA)免疫的小鼠对nOVA或dOVA具有完全交叉反应的DTH,但静脉内给予抗原会诱导出对相应形式特异的Ts。喂食nOVA或dOVA的小鼠对两种形式的OVA具有相同的全身性DTH耐受性,喂食nOVA会诱导脾Ts抑制对nOVA和dOVA的DTH反应。在喂食dOVA的小鼠中未检测到脾Ts。结果支持这样的假设,即喂食天然蛋白质的小鼠全身性DTH耐受性是由于Ts。虽然目前尚无关于Ts在变性蛋白质口服耐受性中作用的补充证据,但本研究与Ts是正常预防因针对膳食蛋白质的DTH引起的肠病的机制这一观点一致。此外,我们的研究强调了口服诱导和胃肠外诱导的Ts之间的差异,并强化了喂食的蛋白质在经肠道或其淋巴附属细胞加工后诱导Ts的观点。