Ginsburg C H, McCluskey R T, Nepom J T, Takaoki M, Falchuk Z M, Benacerraf B, Greene M I
Am J Pathol. 1982 Mar;106(3):421-31.
We have investigated the induction and suppression of granuloma formation elicited by the azobenzenearsonate (ABA) determinant in A/J Mice. ABA-derived syngeneic spleen cells (ABA-SC) administered subcutaneously induced hapten-specific delayed hypersensitivity (DTH), detected by footpad swelling, upon challenge with ABA-bovine serum albumin (BSA) coupled to polyacrylamide beads (PAB). The reactions elicited by ABA-BSA-PAB reached maximal intensity at 24 hours but were relatively persistent and were still marked at 96 hours. Histopathologic examination of footpad responses at 24 and 48 hours after challenge revealed compact collections around beads of mononuclear cells and granulocytes, which were characteristic of DTH reactions. Discrete epithelioid granulomas became apparent by 72 or 96 hours. Unprimed mice or mice primed with ABA-SC and challenged with uncoupled beads did not develop either substantial leukocytic infiltrates or granulomas. Persistent delayed responses were only apparent if the mice were challenged with the homologous hapten-coupled bead, indicating the fine specificity of the reaction. Immune cells were shown to be capable of transferring DTH and granulomatous responsiveness to ABA; the cells were sensitive to anti-Thy 1.2 antiserum and complement, which indicates that the response was thymic-dependent. The intravenous injection of ABA-SC, which is known to induce suppressor cells, prevented the development of DTH or granulomatous responsiveness followinggg subcutaneous immunization with ABA-SC. In addition, the transfer of suspensions containing suppressor T cells into syngeneic mice primed with ABA-SC prevented the development of DTH reactions and granuloma formation followin challenge with ABA-BSA-PAB. Furthermore, only hapten-specific suppressor T cells limited persistent delayed hypersensitivity responses. Having successfully developed granulomas in the footpad, the authors induced and suppressed granulomatous lesions in the gastrointestinal tract in a similar fashion. These experiments establish a model in inbred mice for the study of granulomatous diseases, including those of the gastrointestinal tract.
我们研究了偶氮苯砷酸盐（ABA）决定簇在A/J小鼠中诱导和抑制肉芽肿形成的情况。皮下注射ABA来源的同基因脾细胞（ABA-SC），在用与聚丙烯酰胺珠（PAB）偶联的ABA-牛血清白蛋白（BSA）攻击后，通过足垫肿胀检测到诱导了半抗原特异性迟发型超敏反应（DTH）。ABA-BSA-PAB引发的反应在24小时达到最大强度，但相对持久，在96小时时仍很明显。攻击后24和48小时对足垫反应的组织病理学检查显示，围绕单核细胞和粒细胞珠的致密聚集，这是DTH反应的特征。离散的上皮样肉芽肿在72或96小时时变得明显。未致敏的小鼠或用ABA-SC致敏并用未偶联的珠子攻击的小鼠既没有出现大量白细胞浸润也没有出现肉芽肿。只有在用同源半抗原偶联珠攻击小鼠时，持续的迟发反应才明显，这表明反应具有精细的特异性。免疫细胞被证明能够将DTH和肉芽肿反应性转移给ABA；这些细胞对抗Thy 1.2抗血清和补体敏感，这表明反应是胸腺依赖性的。已知能诱导抑制细胞的ABA-SC静脉注射，可防止在用ABA-SC皮下免疫后DTH或肉芽肿反应性的发展。此外，将含有抑制性T细胞的悬液转移到用ABA-SC致敏的同基因小鼠中，可防止在用ABA-BSA-PAB攻击后DTH反应和肉芽肿形成的发展。此外，只有半抗原特异性抑制性T细胞限制了持续的迟发型超敏反应。在成功地在足垫中形成肉芽肿后，作者以类似的方式在胃肠道中诱导和抑制了肉芽肿病变。这些实验建立了一个近交系小鼠模型，用于研究肉芽肿性疾病，包括胃肠道疾病。
