Kobayashi K, Allred C, Yoshida T
J Immunol. 1985 Nov;135(5):2996-3003.
Pulmonary granulomas were induced in BALB/c mice immunized with methylated bovine serum albumin in complete Freund's adjuvant by the intratracheal injection of plain agarose beads or beads conjugated to specific antigen. Large hypersensitivity granulomas developed around antigen-coupled beads in immunized animals. Smaller but still prominent granulomatous reactions developed around plain beads in immunized mice. In nonimmunized animals, both plain and antigen conjugated beads produced very small granulomas. Granuloma formation in sensitized animals was associated with suppressed delayed-type hypersensitivity reactions induced by the footpad injection of specific and nonspecific antigens. Lymph node cells from sensitized granuloma-bearing mice with cutaneous anergy showed suppressed specific and nonspecific antigen-induced proliferative responses in vitro. These cells also showed suppressed interleukin 2 production in response to specific antigen. Although no soluble suppressive factor was detected in granuloma extracts, suppressor cells were found in lymph nodes of granuloma-bearing mice, which could inhibit antigen-induced production of interleukin 2 by lymph node cells from immunized mice. Antigen-specific immunoglobulin G antibody production was not suppressed in immunized granuloma-bearing mice. Previous studies from our laboratory have demonstrated migration inhibition factor and interleukin 1 activities in aqueous extracts prepared from granuloma-bearing lungs of immunized mice. These results and the findings reported here indicate that granuloma formation and the associated anergy observed in this system are primarily expressions of cell-mediated immunity; selective suppression of in vivo and in vitro expressions of cell-mediated immunity in granuloma-bearing mice may be due to impaired antigen-induced interleukin 2 production; and such impairment is caused by suppressor cells.
通过气管内注射普通琼脂糖珠或与特定抗原偶联的珠子，在以完全弗氏佐剂免疫甲基化牛血清白蛋白的BALB/c小鼠中诱导肺肉芽肿形成。在免疫动物中，抗原偶联珠周围形成了大的超敏肉芽肿。在免疫小鼠中，普通珠子周围也出现了较小但仍很明显的肉芽肿反应。在未免疫的动物中，普通珠子和抗原偶联珠均产生非常小的肉芽肿。致敏动物中的肉芽肿形成与足垫注射特异性和非特异性抗原诱导的迟发型超敏反应受到抑制有关。来自患有肉芽肿且皮肤无反应性的致敏小鼠的淋巴结细胞在体外显示出特异性和非特异性抗原诱导的增殖反应受到抑制。这些细胞对特异性抗原的反应中也显示出白细胞介素2产生受到抑制。尽管在肉芽肿提取物中未检测到可溶性抑制因子，但在患有肉芽肿的小鼠的淋巴结中发现了抑制细胞，其可以抑制免疫小鼠的淋巴结细胞对抗原诱导的白细胞介素2的产生。在患有肉芽肿的免疫小鼠中，抗原特异性免疫球蛋白G抗体的产生未受到抑制。我们实验室先前的研究已证明，从免疫小鼠的患有肉芽肿的肺中制备的水提取物中具有迁移抑制因子和白细胞介素1活性。这些结果以及此处报道的发现表明，在该系统中观察到的肉芽肿形成和相关的无反应性主要是细胞介导的免疫的表现；患有肉芽肿的小鼠体内和体外细胞介导的免疫表达的选择性抑制可能是由于抗原诱导的白细胞介素2产生受损；而这种损伤是由抑制细胞引起的。
