Voisin G A, Kinsky R G, Duc H T
J Exp Med. 1972 May 1;135(5):1185-203. doi: 10.1084/jem.135.5.1185.
CBA mice were rendered highly tolerant to A/Jax cells by neonatal intravenous injections of (CBA x A)F(1) spleen cells. The high degree of tolerance was ascertained by the absence of circulating antibodies detected in the sera by the usual tests and by the perfect state of A skin grafts during all the experiments. Tolerant sera (sera from tolerant animals) were studied at three periods of tolerance: before skin test grafting, from 2 to 11 wk after grafting, and at time of sacrifice at almost 6 months of age. The tolerant sera were shown to have specific facilitation-enhancing properties promoting the take and growth of A/Jax sarcoma (SaI and /Sa 15091a grafted on normal CBA mice. These properties were present throughout the duration of the experiments, showing that they were not the result of a beginning interruption of tolerance. The tolerant sera, although lacking the usual serological properties (hemagglutination, hemolysis, cytotoxicity, passive cutaneous anaphylaxis) had, however, specific synergistic hemagglutinating properties (increasing the hemagglutinating titer of a reference immune serum). Antibodies giving direct specific hemagglutination could be extracted from spleens of 20% of highly tolerant mice. The tolerant sera were also found to contain more IgG1 and more IgA than normal sera while they contained normal quantities of the complement-fixing immunoglobulins IgG2 and IgM. Fractionation of tolerant sera on DEAE chromatography column confirmed the data concerning immunoglobulin classes and demonstrated direct specific serological activities undetected in unfractionated sera: a weak hemolysis in the most cationic fractions and a weak hemagglutination in the middle fractions. Synergistic hemagglutination, detected in unfractionated serum, was localized in fast anionic fractions containing high IgA concentration, along with facilitation-enhancing activity, thus confirming a link suggested previously between these three properties. The relation between immunological tolerance and facilitating antibodies was discussed in the light of the fact that antibodies, possibly of a particular class continuously present at low dose in the sera of highly tolerant animals, are able to transfer (at least partly) this state of tolerance provided a sensitive test system is utilized.
通过新生期静脉注射（CBA×A）F1脾细胞，使CBA小鼠对A/Jax细胞产生高度耐受性。通过常规检测未在血清中检测到循环抗体，以及在所有实验过程中A皮肤移植的完美状态，确定了高度耐受性。在耐受的三个阶段研究了耐受血清（来自耐受动物的血清）：皮肤试验移植前、移植后2至11周以及在近6个月龄处死时。结果表明，耐受血清具有促进A/Jax肉瘤（移植到正常CBA小鼠上的SaI和/Sa 15091a）存活和生长的特异性促进增强特性。这些特性在整个实验过程中都存在，表明它们不是耐受开始中断的结果。耐受血清虽然缺乏通常的血清学特性（血凝、溶血、细胞毒性、被动皮肤过敏反应），但具有特异性协同血凝特性（提高参考免疫血清的血凝滴度）。可以从20%的高度耐受小鼠的脾脏中提取出产生直接特异性血凝的抗体。还发现耐受血清比正常血清含有更多的IgG1和更多的IgA，而补体结合免疫球蛋白IgG2和IgM的含量正常。在DEAE层析柱上对耐受血清进行分级分离，证实了有关免疫球蛋白类别的数据，并证明了在未分级血清中未检测到的直接特异性血清学活性：在最具阳离子性的级分中有微弱的溶血，在中间级分中有微弱的血凝。在未分级血清中检测到的协同血凝作用，定位在含有高浓度IgA的快速阴离子级分中，同时伴有促进增强活性，从而证实了先前提出的这三种特性之间的联系。鉴于在高度耐受动物的血清中可能持续低剂量存在特定类别的抗体，并且只要利用敏感的检测系统，这些抗体就能够（至少部分地）传递这种耐受状态，因此讨论了免疫耐受与促进抗体之间的关系。
