Sonozaki H, Papermaster V, Yoshida T, Cohen S
J Immunol. 1975 Dec;115(6):1657-61.
Guinea pigs exhibiting delayed hypersensitivity may be desensitized by a single large dose of antigen administered intramuscularly. In the present experiments, desensitization with a soluble protein such as egg albumin (EA) or bovine gamma-globulin (BGG) was nonspecific in that they suppressed both cutaneous reactivity and the macrophage disappearance reaction (MDR) to unrelated antigen in doubly immunized animals. In contrast, myobacterial antigen, at the dose studied, showed limited specificity in that it could suppress the MDR but not a skin test to an unrelated antigen. Induction of an MDR was shown to be associated with the appearance of macrophage migration inhibitory factor (MIF) and chemotactic activity in the peritoneal exudate fluid. Pretreatment with desensitizing doses of mycobacteria prevented the EA-induced appearance of MIF in the peritoneal fluids. In contrast, chemotactic activity could still be recovered, even though the MDR was suppressed. Mycobacteria functioned as a specific desensitizer not only with respect to cutaneous reactivity, as stated above, but also with respect to the production of chemotatic factor by peritoneal exudate cells. In contrast, mycobacteria functioned as a nonspecific desensitizer with respect to both the MDR and MIF production. These results suggest that the MDR may be an in vivo manifestation of MIF activity, whereas the cutaneous delayed hypersensitivity reaction may be more dependent upon chemotactic activity. These observations reported here, taken in conjunction with previously described in vitro studies, suggest that desensitization is a complex phenomenon which may be the result of several different mechanisms acting separately or in concert. The apparent discrepancies in the literature as to whether or not desensitization is a specific process would appear to arise from differences in the experimental model and the particular antigen used.
表现出迟发型超敏反应的豚鼠可通过肌肉注射一剂大剂量抗原实现脱敏。在本实验中,用可溶性蛋白质如卵清蛋白(EA)或牛γ球蛋白(BGG)进行脱敏是非特异性的,因为它们抑制了双重免疫动物对无关抗原的皮肤反应性和巨噬细胞消失反应(MDR)。相比之下,在所研究的剂量下,分枝杆菌抗原则表现出有限的特异性,即它可以抑制MDR,但不能抑制对无关抗原的皮肤试验。已表明MDR的诱导与巨噬细胞迁移抑制因子(MIF)的出现以及腹膜渗出液中的趋化活性有关。用脱敏剂量的分枝杆菌进行预处理可防止EA诱导的腹膜液中MIF的出现。相比之下,即使MDR受到抑制,趋化活性仍可恢复。分枝杆菌不仅如上所述对皮肤反应性起特异性脱敏剂的作用,而且对腹膜渗出细胞产生趋化因子也起特异性脱敏剂的作用。相比之下,分枝杆菌对MDR和MIF的产生起非特异性脱敏剂的作用。这些结果表明,MDR可能是MIF活性的体内表现,而皮肤迟发型超敏反应可能更依赖于趋化活性。此处报道的这些观察结果,结合先前描述的体外研究,表明脱敏是一种复杂的现象,可能是几种不同机制单独或共同作用的结果。文献中关于脱敏是否是一个特异性过程的明显差异似乎源于实验模型和所用特定抗原的差异。