Otsuka Atsushi, Matsunaga Isamu, Komori Takaya, Tomita Kadusa, Toda Yoshinobu, Manabe Toshiaki, Miyachi Yoshiki, Sugita Masahiko
Laboratory of Cell Regulation, Institute for Virus Research, Kyoto University, Kyoto, Japan.
J Immunol. 2008 Dec 15;181(12):8528-33. doi: 10.4049/jimmunol.181.12.8528.
Delayed-type hypersensitivity represents high levels of protein Ag-specific adaptive immunity induced by mycobacterial infection, and can be monitored in the Ag-challenged skin. Besides protein Ags, recent evidence has suggested that a substantial immunity directed against glycolipid Ags is also elicited in response to mycobacterial infection, but skin hypersensitivity to this class of Ags has not been fully assessed. To address this issue directly, glycolipid-specific skin reactions were evaluated in guinea pigs infected with Mycobacterium avium complex (MAC). Significant skin induration was observed in MAC-infected, but not mock-infected, guinea pigs, following intradermal administration of a mixture of MAC-derived glycolipids. Surprisingly, this glycolipid-specific skin response involved up-regulated expression of IL-5 mRNA in situ and marked local infiltration of eosinophils. Challenge experiments with individual glycolipid components detected an outstanding capability for trehalose dimycolate (TDM), but not a structurally related glycolipid, glucose monomycolate, to elicit the skin response. T lymphocytes derived from the spleen of MAC-infected, but not uninfected, guinea pigs specifically responded to TDM in vitro by up-regulating IL-5 transcription, and this response was not blocked by Abs that reacted to the known guinea pig group 1 CD1 proteins. Finally, the eosinophilic skin hypersensitivity to TDM was also elicited in guinea pigs vaccinated with bacillus Calmette-Guerin, which contrasted sharply with the classical delayed-type hypersensitivity response to the purified protein derivative. Therefore, the TDM-elicited eosinophilic response defines a new form of hypersensitivity in mycobacterial infection, which may account for local infiltration of eosinophils often observed at the site of infection.
迟发型超敏反应代表由分枝杆菌感染诱导的高水平蛋白质抗原特异性适应性免疫，并且可以在抗原激发的皮肤中进行监测。除了蛋白质抗原外，最近的证据表明，针对糖脂抗原的大量免疫反应也会在分枝杆菌感染后引发，但皮肤对这类抗原的超敏反应尚未得到充分评估。为了直接解决这个问题，我们在感染鸟分枝杆菌复合体（MAC）的豚鼠中评估了糖脂特异性皮肤反应。在皮内注射MAC衍生的糖脂混合物后，在感染MAC的豚鼠中观察到明显的皮肤硬结，而在假感染的豚鼠中未观察到。令人惊讶的是，这种糖脂特异性皮肤反应涉及原位IL-5 mRNA表达上调和嗜酸性粒细胞的显著局部浸润。对单个糖脂成分的激发实验检测到海藻糖二霉菌酸酯（TDM）具有出色的引发皮肤反应的能力，但结构相关的糖脂单霉菌酸葡萄糖则没有。来自感染MAC但未感染的豚鼠脾脏的T淋巴细胞在体外通过上调IL-5转录对TDM产生特异性反应，并且这种反应不会被与已知豚鼠1组CD1蛋白反应的抗体阻断。最后，在用卡介苗接种的豚鼠中也引发了对TDM的嗜酸性皮肤超敏反应，这与对纯化蛋白衍生物的经典迟发型超敏反应形成鲜明对比。因此，TDM引发的嗜酸性反应定义了分枝杆菌感染中超敏反应的一种新形式，这可能解释了在感染部位经常观察到的嗜酸性粒细胞局部浸润现象。
