SUPPRESSOR T-CELLS GENERATED BY ORAL TOLERIZATION TO MYELIN BASIC-PROTEIN SUPPRESS BOTH INVITRO AND INVIVO IMMUNE-RESPONSES BY THE RELEASE OF TRANSFORMING GROWTH-FACTOR-BETA AFTER ANTIGEN-SPECIFIC TRIGGERING
SUPPRESSOR T-CELLS GENERATED BY ORAL TOLERIZATION TO MYELIN BASIC-PROTEIN SUPPRESS BOTH INVITRO AND INVIVO IMMUNE-RESPONSES BY THE RELEASE OF TRANSFORMING GROWTH-FACTOR-BETA AFTER ANTIGEN-SPECIFIC TRIGGERING
复制标题
DOI：
10.1073/pnas.89.1.421
复制
发表时间：
1992-01-01
影响因子：
11.1
通讯作者：
WEINER, HL
中科院分区：
文献类型：
--
作者：
MILLER, A;LIDER, O;WEINER, HL
口服髓鞘碱性蛋白是抑制实验性自身免疫性脑脊髓炎的有效方法。我们之前已经证明，这种抑制是由CD8+T细胞介导的，CD8+T细胞在体外过继转移保护和抑制免疫反应。在本研究中，我们发现口服耐受MBP的动物的调节器细胞在体外经MBP刺激后产生一种抑制因子，该抑制因子可被抗转化生长因子-β(TGF-β)中和抗体特异性抑制。干扰素抗体、肿瘤坏死因子α/β抗体或消炎痛抗体均未观察到效果。此外，口服MBP或卵清蛋白刺激后的动物细胞培养上清液中可直接显示1型转化生长因子-β-1亚型(TGF-β-1)的活性形式。体内注射转化生长因子-β1抗血清可阻断口服耐受对EAE大鼠MBP的保护作用。此外，向不耐受的EAE动物注射抗转化生长因子-β1血清会导致疾病严重程度和病程的增加。这些结果表明，口服MBP耐受和自然恢复机制诱导的EAE的免疫调节使用依赖于转化生长因子-β-1的共同免疫调节途径。这种关联对人类自身免疫性疾病具有治疗意义，并可能有助于解释T细胞主动抑制的中介机制之一。
Oral administration of myelin basic protein (MBP) is an effective way of suppressing experimental autoimmune encephalomyelitis (EAE). We have previously shown that such suppression is mediated by CD8+ T cells, which adoptively transfer protection and suppress immune responses in vitro. In the present study we have found that modulator cells from animals orally tolerized to MBP produce a suppressor factor upon stimulation with MBP in vitro that is specifically inhibited by anti-transforming growth factor-beta (TGF-beta) neutralizing antibodies. No effect was observed with antibodies to gamma-interferon, tumor necrosis factor-alpha/beta, or indomethacin. In addition, the active form of the type 1 isoform of TGF-beta-1 (TGF-beta-1) can be directly demonstrated in the supernatants of cells from animals orally tolerized to MBP or ovalbumin after antigen stimulation in vitro. Antiserum specific for TGF-beta-1 administered in vivo abrogated the protective effect of oral tolerization to MBP in EAE. Furthermore, injection of anti-TGF-beta-1 serum to nontolerized EAE animals resulted in an increase in severity and duration of disease. These results suggest that immunomodulation of EAE induced by oral tolerization to MBP and natural recovery mechanisms use a common immunoregulatory pathway that is dependent on TGF-beta-1. Implications of such an association are of therapeutic relevance to human autoimmune diseases and may help to explain one of the mechanisms involved in the mediation of active suppression by T cells.