Albers R, de Heer C, Bol M, Bleumink R, Seinen W, Pieters R
Research Institute for Toxicology, Utrecht University, The Netherlands.
Eur J Immunol. 1998 Apr;28(4):1233-42. doi: 10.1002/(SICI)1521-4141(199804)28:04<1233::AID-IMMU1233>3.0.CO;2-G.
Exposure to certain drugs and environmental chemicals can provoke the onset of autoimmune disease in susceptible individuals by releasing (self) epitopes for which tolerance has not been established, while simultaneously providing the necessary adjuvant activity. The resulting response type is influenced by the genotype of exposed individuals and relates to susceptibility to the adverse immune effects of the chemicals. Here, we assessed the modulatory role of the chemical compounds themselves. A single injection of streptozotocin (STZ) increased the number of CD8+ cells, macrophages, apoptotic cells, and IFN-gamma-producing T helper and T cytotoxic cells, whereas the number of CD4+ cells and B cells was reduced in the draining lymph node. Coinjection with the reporter antigen TNP-OVA resulted in primary and secondary production of TNP-specific antibodies that were predominantly of IgG2a and IgG2b isotype, whereas STZ did not enhance priming for delayed-type hypersensitivity (DTH) responses to TNP-OVA. Injection of HgCl2 on the other hand, reduced the number of IFN-gamma-producing cells, induced accumulation of B cells and CD4+ and CD8+ T cells, enhanced IgG1 and IgE production to TNP-OVA, and primed for secondary IgG1 and IgE production as well as for DTH reactions. Together these results indicate that a single injection of STZ stimulates type-1 responses, whereas HgCl2 enhanced mixed type-1 and -2 responses in BALB/c mice. These response types match the (auto)immune effects elicited to unknown (auto)antigens following multiple injections of these chemicals.
接触某些药物和环境化学物质可通过释放尚未建立耐受性的（自身）表位，同时提供必要的佐剂活性，从而在易感个体中引发自身免疫性疾病。所产生的反应类型受暴露个体基因型的影响，并与对化学物质不良免疫效应的易感性有关。在此，我们评估了这些化合物本身的调节作用。单次注射链脲佐菌素（STZ）可增加引流淋巴结中CD8 +细胞、巨噬细胞、凋亡细胞以及产生干扰素-γ的辅助性T细胞和细胞毒性T细胞的数量，而CD4 +细胞和B细胞的数量则减少。与报告抗原TNP-OVA共同注射可导致TNP特异性抗体的初次和二次产生，这些抗体主要为IgG2a和IgG2b同种型，而STZ并未增强对TNP-OVA的迟发型超敏反应（DTH）的致敏作用。另一方面，注射氯化汞可减少产生干扰素-γ的细胞数量，诱导B细胞以及CD4 +和CD8 + T细胞的积累，增强对TNP-OVA的IgG1和IgE产生，并引发二次IgG1和IgE产生以及DTH反应。这些结果共同表明，单次注射STZ可刺激1型反应，而氯化汞可增强BALB/c小鼠的1型和2型混合反应。这些反应类型与多次注射这些化学物质后对未知（自身）抗原引发的（自身）免疫效应相匹配。
