Klinkhammer C, Popowa P, Gleichmann H
Clinical Department, University of Düsseldorf, Federal Republic of Germany.
Diabetes. 1988 Jan;37(1):74-80. doi: 10.2337/diab.37.1.74.
The mechanism(s) of the immunological reactions involved in the pathogenesis of hyperglycemia induced by multiple intraperitoneal injections of subdiabetogenic doses of streptozocin (STZ) in mice remains to be elucidated. We found that STZ can act as a hapten in vivo by using the popliteal lymph node (PLN) assay. With this assay a direct toxic effect of STZ on the pancreatic beta-cells was dissociated from the effects exerted on the immune system. Subcutaneous injections of STZ induced immune reactivity in the draining PLN as determined by increase in weight, cell number, and [3H]thymidine incorporation. T-lymphocytes were required to induce the PLN response to STZ, because athymic nu/nu mice completely failed to respond to STZ, in contrast to their euthymic +/nu counterparts (P less than .001). The STZ-induced PLN response was sex independent and unaffected by prior subcutaneous injections of 3-O-methylglucose known to protect pancreatic beta-cells against STZ. STZ-primed mice exhibited an accelerated and enhanced STZ-specific secondary PLN response on challenge with subimmunogenic doses of STZ. In adoptive transfer experiments, STZ-sensitized splenic lymphocytes enriched for T-lymphocytes induced an STZ-specific significant (P less than .005) PLN enlargement provided the syngeneic recipients had been pretreated with subimmunogenic doses of STZ. Presumably, such STZ-specific immune reactions enhance a subtoxic effect of STZ on the pancreatic beta-cells.
多次腹腔注射亚致糖尿病剂量的链脲佐菌素（STZ）诱导小鼠高血糖发病机制中涉及的免疫反应机制仍有待阐明。我们发现，通过腘淋巴结（PLN）试验，STZ在体内可作为半抗原。通过该试验，STZ对胰腺β细胞的直接毒性作用与对免疫系统的作用得以区分。皮下注射STZ可诱导引流PLN中的免疫反应性，这可通过重量增加、细胞数量增加和[3H]胸腺嘧啶核苷掺入来确定。诱导PLN对STZ的反应需要T淋巴细胞，因为无胸腺裸鼠（nu/nu）对STZ完全无反应，而与其有胸腺的同基因对照小鼠（+/nu）形成对比（P<0.001）。STZ诱导的PLN反应与性别无关，且不受先前皮下注射已知可保护胰腺β细胞免受STZ损伤的3-O-甲基葡萄糖的影响。用亚免疫原剂量的STZ攻击时，用STZ预处理的小鼠表现出加速且增强的STZ特异性继发性PLN反应。在过继转移实验中，如果同基因受体预先用亚免疫原剂量的STZ进行预处理，富含T淋巴细胞的经STZ致敏的脾淋巴细胞可诱导STZ特异性的显著（P<0.005）PLN肿大。据推测，这种STZ特异性免疫反应会增强STZ对胰腺β细胞的亚毒性作用。
