Hamaoka T, Yoshizawa M, Yamamoto H, Kuroki M, Kitagawa M
J Exp Med. 1977 Jul 1;146(1):91-106. doi: 10.1084/jem.146.1.91.
An experimental condition was established in vivo for selectively eliminating hapten-reactive suppressor T-cell activity generated in mice primed with a para-azobenzoate (PAB)-mouse gamma globulin (MGG)-conjugate and treated with PAB-nonimmunogenic copolymer of D-amino acids (D- glutamic acid and D-lysine; D-GL). The elimination of suppressor T-cell activity with PAB-D-GL treatment from the mixed populations of hapten- reactive suppressor and helper T cells substantially increased apparent helper T-cell activity. Moreover, the inhibition of PAB-reactive suppressor T-cell generation by the pretreatment with PAB-D-GL before the PAB-MGG-priming increased the development of PAB-reactive helper T-cell activity. The analysis of hapten-specificity of helper T cells revealed that the reactivity of helper cells developed in the absence of suppressor T cells was more specific for primed PAB-determinants and their cross-reactivities to structurally related determinants such as meta-azobenzoate (MAB) significantly decreased, as compared with the helper T-cell population developed in the presence of suppressor T lymphocytes. In addition, those helper T cells generated in the absence of suppressor T cells were highly susceptible to tolerogenesis by PAB-D- GL. Similarly, the elimination of suppressor T lymphocytes also enhanced helper T-cell activity in a polyclonal fashion in the T-T cell interactions between benzylpenicilloyl (BPO)-reactive T cells and PAB- reactive T cells after immunization of mice with BPO-MGG-PAB. Thus inhibition of BPO-reactive suppressor T-cell development by the BPO-v-GL- pretreatment resulted in augmented generation of PAB-reactive helper T cells with higher susceptibility of tolerogenesis to PAB-D-GL. Thus, these results support the notion that suppressor T cells eventually suppress helper T-cell activity and indicate that the function of suppressor T cells related to helper T-cell development is to inhibit the increase in the specificity and apparent affinity of helper T cells in the primary immune response. The hapten-reactive suppressor and helper T lymphocytes are considered as a model system of T cells that regulate the immune response, and the potential applicability of this system to manipulating various T cell-mediated immune responses is discussed in this context.
建立了一种体内实验条件，用于选择性消除在用对氨基苯甲酸酯（PAB）-小鼠γ球蛋白（MGG）偶联物致敏并用PAB-D-氨基酸非免疫原性共聚物（D-谷氨酸和D-赖氨酸；D-GL）处理的小鼠中产生的半抗原反应性抑制性T细胞活性。用PAB-D-GL处理从半抗原反应性抑制性T细胞和辅助性T细胞的混合群体中消除抑制性T细胞活性，可显著提高表观辅助性T细胞活性。此外，在PAB-MGG致敏前用PAB-D-GL预处理抑制PAB反应性抑制性T细胞的产生，可增加PAB反应性辅助性T细胞活性的发展。对辅助性T细胞半抗原特异性的分析表明，与在抑制性T淋巴细胞存在下发育的辅助性T细胞群体相比，在没有抑制性T细胞的情况下发育的辅助性细胞对致敏PAB决定簇的反应性更强，并且它们与结构相关决定簇如间氨基苯甲酸酯（MAB）的交叉反应性显著降低。此外，在没有抑制性T细胞的情况下产生的那些辅助性T细胞对PAB-D-GL诱导的耐受形成高度敏感。同样，在用苄青霉素酰基（BPO）-MGG-PAB免疫小鼠后，在BPO反应性T细胞和PAB反应性T细胞之间的T-T细胞相互作用中，消除抑制性T淋巴细胞也以多克隆方式增强了辅助性T细胞活性。因此，BPO-v-GL预处理抑制BPO反应性抑制性T细胞的发育，导致产生对PAB-D-GL耐受形成敏感性更高的PAB反应性辅助性T细胞增加。因此，这些结果支持抑制性T细胞最终抑制辅助性T细胞活性的观点，并表明与辅助性T细胞发育相关的抑制性T细胞功能是在初次免疫反应中抑制辅助性T细胞特异性和表观亲和力的增加。半抗原反应性抑制性和辅助性T淋巴细胞被认为是调节免疫反应的T细胞模型系统，并在此背景下讨论了该系统在操纵各种T细胞介导的免疫反应中的潜在适用性。
