INDUCTION OF ANERGY OR ACTIVE SUPPRESSION FOLLOWING ORAL TOLERANCE IS DETERMINED BY ANTIGEN DOSAGE
INDUCTION OF ANERGY OR ACTIVE SUPPRESSION FOLLOWING ORAL TOLERANCE IS DETERMINED BY ANTIGEN DOSAGE
复制标题
DOI：
10.1073/pnas.91.14.6688
复制
发表时间：
1994-07-05
影响因子：
11.1
通讯作者：
WEINER, HL
中科院分区：
文献类型：
--
作者：
FRIEDMAN, A;WEINER, HL
通过低剂量（1 mg）或高剂量（5-20 mg）喂养方案，小鼠对鸡蛋白色溶菌酶或大鼠对豚鼠髓鞘碱性蛋白产生口服耐受性。高剂量的抗原诱导的耐受性的特征是无反应性，很少或没有主动抑制和白细胞介素4（IL-4）的分泌增加。无反应性表现为在重组IL-2中培养后IL-2分泌细胞的频率增加。低剂量抗原诱导的耐受性的特征在于抗原驱动的主动抑制，伴随转化生长因子β（TGF-β）和IL-4的分泌增加以及最小的无反应性。在没有进一步免疫的情况下，来自通过两种方案口服耐受的动物的脾细胞以抗原特异性方式分泌增加水平的IL-4和TGF-β。喂食高剂量的动物分泌更多的IL-4和更少的TGF-β，而喂食低剂量的动物分泌更多的TGF-β和更少的IL-4。这些结果表明，两种饲养方案诱导的细胞群在其细胞因子分泌谱和其体外主动抑制和诱导无反应性的能力方面不同。我们的研究结果为区分不同形式的抗原驱动的外周耐受提供了基础，并对口服诱导的抗原特异性调节人类自身免疫性疾病具有重要意义。
Oral tolerance was generated to hen egg white lysozyme in the mouse or to guinea pig myelin basic protein in the rat by a low-dose (1 mg) or a high dose (5-20 mg) feeding regimen. High doses of antigen induced tolerance characterized by anergy with little or no active suppression and increased secretion of interleukin 4 (IL-4). Anergy was shown by an increase in frequency of IL-2-secreting cells following culture in recombinant IL-2. Low doses of antigen induced tolerance characterized by antigen-driven active suppression with increased secretion of transforming growth factor beta (TGF-beta) and IL-4 and minimal anergy. Without further immunization, spleen cells from animals orally tolerized by both regimens secreted increased levels of IL-4 and TGF-beta in an antigen specific manner. Animals fed high doses secreted more IL-4 and less TGF-beta, whereas those fed low doses secreted more TGF-beta and less IL-4. These results demonstrate that the two feeding regimens induced cell populations that differed in their cytokine secretion profile and their capacity to actively suppress in vitro and to induce anergy. Our results provide a basis for distinguishing different forms of antigen-driven peripheral tolerance and have important implications for orally induced antigen-specific modulation of human autoimmune diseases.