Kataria Y P, Holter J F
Department of Medicine, East Carolina University School of Medicine, Greenville, North Carolina, USA.
Clin Chest Med. 1997 Dec;18(4):719-39. doi: 10.1016/s0272-5231(05)70415-9.
Because of its association with cutaneous anergy, sarcoidosis was originally viewed as a defect of cellular immunity. Supporting that misperception were early studies of peripheral blood lymphocytes that found lymphopenia and impaired lymphocyte responses to mitogens and recall antigens. The clue to a vast underlying network of complex hyperactive cellular immune functions was discovered in the paradoxical finding of in vitro spontaneous lymphoblastic transformation and lymphokine production. Subsequently, investigative focus shifted to the activated, proliferating T-helper lymphocytes, the lymphokines of which were found to function in the recruitment and retention of monocytes for granuloma development. T-helper lymphocytes also contributed to the mechanism of hypergammaglobulinemia through their influence on B cells. The most intriguing question about sarcoid immunology is the initiating factor that triggers the T-lymphocyte activation and proliferation in the first place. There is much to suggest that antigen processing and presentation launches the process. Because lymphocyte activation and proliferation antedate granuloma formation at K-S skin test sites and in the lung, we combined the harvesting technique of BAL with the K-S bioassay to show that granulomagenic antigen is being processed by monocyte-macrophages. The finding of autologous monocyte-macrophage granulomagenicity raises the distinct possibility that sarcoidosis is a unique cell-mediated type of autoimmune process. The isolation and identification of the granulomagenic factor is the exciting research frontier ahead.
由于结节病与皮肤无反应性相关，它最初被视为细胞免疫缺陷。早期对外周血淋巴细胞的研究支持了这种误解，这些研究发现淋巴细胞减少以及淋巴细胞对丝裂原和回忆抗原的反应受损。体外自发淋巴细胞转化和淋巴因子产生这一矛盾发现揭示了复杂的高活性细胞免疫功能背后庞大的潜在网络线索。随后，研究重点转向活化、增殖的辅助性T淋巴细胞，发现其淋巴因子在募集和保留单核细胞以促进肉芽肿形成中发挥作用。辅助性T淋巴细胞还通过对B细胞的影响促成了高球蛋白血症的机制。关于结节病免疫学最引人入胜的问题是首先触发T淋巴细胞活化和增殖的起始因素。有很多迹象表明抗原加工和呈递启动了这一过程。由于在Kveim-Siltzbach皮肤试验部位和肺部，淋巴细胞活化和增殖早于肉芽肿形成，我们将支气管肺泡灌洗（BAL）的采集技术与Kveim-Siltzbach生物测定法相结合，以表明肉芽肿性抗原正在被单核细胞-巨噬细胞加工处理。自体单核细胞-巨噬细胞具有肉芽肿形成能力这一发现增加了结节病是一种独特的细胞介导型自身免疫过程的显著可能性。分离和鉴定肉芽肿形成因子是未来令人兴奋的研究前沿。
