Hamaoka T, Yamaskita U, Takami T, Kitagawa M
J Exp Med. 1975 Jun 1;141(6):1308-28. doi: 10.1084/jem.141.6.1308.
Treatment of a p-azobenzoate (PAB) derivative of a copolymer of D-glutamic acid and D-lysine (D-GL) induced a profound state of unresponsiveness to PAB-reactive helper T lymphocytes generated in PAB-mouse gamma globulin (MGG)-primed mice. This unresponsiveness in T lymphocytes was specific for PAB-reactive cells, since the bacterial alpha-amylase-, keyhole limpet hemocyanin-, or ovalbumin-primed helper T lymphocytes were not suppressed by PAB-D-GL treatment. Taking advantage of the relative ease with which PAB-D-GL can induce specific unresponsiveness to helper T lymphocytes in an animal previously primed with PAB-MGG, it was possible to approach certain questions concerning the mechanisms of tolerance-induction and the fate of tolerant helper T lymphocytes in the PAB-D-GL model by utilizing a classical adoptive cell transfer systemmelimination of the possibility of carry-over of the tolerogen with cells or of the generation of suppressor cells as the result of PAB-D-GL treatment as an explanation of the suppression of helper T-cell activity strongly inplicates the existence of a central intracellular mechanism of specific tolerance on the helper T-cell level. The possibility that suppression of the activity of PAB-reactive helper T lymphocytes by PAB-D-GL reflects simple blocking of surface receptor molecules on T lymphocytes was ruled out as it was found that the helper activity of PAB-reactive cells was minimally suppressed even when PAB-D-GL was directly exposed in vitro to helper T lymphocytesmmoreover, the most conclusive evidence on te the tolerant state induced by in vivo exposure of primed T cells to PAB-D-GL. It appears, therefore, that specific tolerance induced by PAB-D-GL' TO PAB-reactive helper T lymphocytes is an example of irreversible inhibition of T-cell reactivity to antigen, reflecting yet to be determined events at the intra- and subcellular levels.
D-谷氨酸和D-赖氨酸共聚物（D-GL）的对氨基苯甲酸酯（PAB）衍生物的处理诱导了对在PAB-小鼠γ球蛋白（MGG）致敏小鼠中产生的PAB反应性辅助性T淋巴细胞的深度无反应状态。T淋巴细胞中的这种无反应性对PAB反应性细胞具有特异性，因为细菌α-淀粉酶、钥孔戚血蓝蛋白或卵清蛋白致敏的辅助性T淋巴细胞不会被PAB-D-GL处理所抑制。利用PAB-D-GL在先前用PAB-MGG致敏的动物中相对容易诱导对辅助性T淋巴细胞的特异性无反应性这一特点，通过使用经典的过继性细胞转移系统，有可能探讨关于耐受诱导机制以及PAB-D-GL模型中耐受辅助性T淋巴细胞命运的某些问题，排除了耐受原随细胞携带或PAB-D-GL处理导致抑制性细胞产生作为辅助性T细胞活性抑制解释的可能性，这强烈暗示了在辅助性T细胞水平存在特异性耐受的中心细胞内机制。PAB-D-GL对PAB反应性辅助性T淋巴细胞活性的抑制反映T淋巴细胞表面受体分子简单阻断的可能性被排除，因为发现即使PAB-D-GL在体外直接暴露于辅助性T淋巴细胞，PAB反应性细胞的辅助活性也只是轻微被抑制，此外，关于经体内用PAB-D-GL暴露致敏的T细胞诱导的耐受状态的最确凿证据。因此，似乎PAB-D-GL诱导的对PAB反应性辅助性T淋巴细胞的特异性耐受是T细胞对抗原反应不可逆抑制的一个例子，反映了细胞内和亚细胞水平尚未确定的事件。
