Wands J R, Perrotto J L, Alpert E, Isselbacher K J
J Clin Invest. 1975 May;55(5):921-9. doi: 10.1172/JCI108021.
Peripheral lymphocytes from patients with hepatitis-B surface antigen (HBsAg)-positive and -negative acute hepatitis (AH), chronic active hepatitis (CAH), chronic persistent hepatitis (CPH), and normal controls were tested for in vitro cytotoxicity and blast transformation. Cytotoxicity was measured by chrominum (21Cr) release into the medium from 51Cr-labeled Chang liver cells after incubation for 6 h with peripheral lymphocytes at a lymphocyte target cell ratio of 200:1. Concomitant 72-h incubation studies were performed to assess thymus cell-dependent (T) lymphocyte function as measured by conccanavalin A (Con A)- stimulated incorporation of tritiated thymidine (blast transformation) and by cytotoxicity. It was found that (a) lymphocytes from patients with AH are cytotoxic to Chang liver cells compared to controls (P less than 0.001); (b) lymphocytes from patients with acute and chronic hepatitis are less cytotoxic when incubated with autologous and homologous HB2Ag-positive and -negative AH, CAH, and CPH are as cytotoxic as normal controls when stimulated with a nonspecific mitogen such as Con A; and (d) lymphocytes from patients with CAH while on prednisone therapy showed marked depression of cytotoxicity when stimulated with Con A. Thus these studies show that patients with AH have circulating T lymphocytes which are capable of causing the destruction of Chang liver cells. There is no defect in T-cell function as measured by Con A-stimulated cytotoxicity. There is a serum factor (s) in patients with acute and chronic hepatitis which inhibits spontaneous and induced lymphocyte cytotoxicity and blast transformation. Finally, prednisone treatment appears to inhibit lymphocyte cytotoxicity in patients with CAH.
对乙型肝炎表面抗原(HBsAg)阳性和阴性的急性肝炎(AH)、慢性活动性肝炎(CAH)、慢性持续性肝炎(CPH)患者以及正常对照的外周淋巴细胞进行体外细胞毒性和母细胞转化测试。细胞毒性通过在淋巴细胞与靶细胞比例为200:1的条件下,外周淋巴细胞与51Cr标记的Chang肝细胞孵育6小时后,铬(21Cr)释放到培养基中的量来测定。同时进行72小时的孵育研究,以评估通过伴刀豆球蛋白A(Con A)刺激的氚化胸腺嘧啶核苷掺入(母细胞转化)和细胞毒性所测量的胸腺细胞依赖性(T)淋巴细胞功能。结果发现:(a)与对照组相比,AH患者的淋巴细胞对Chang肝细胞具有细胞毒性(P小于0.001);(b)急性和慢性肝炎患者的淋巴细胞在与自身和同源的HBsAg阳性和阴性的AH、CAH和CPH孵育时细胞毒性较低,在用非特异性有丝分裂原如Con A刺激时,其细胞毒性与正常对照相同;(d)接受泼尼松治疗的CAH患者的淋巴细胞在用Con A刺激时显示出明显的细胞毒性降低。因此,这些研究表明,AH患者具有能够导致Chang肝细胞破坏的循环T淋巴细胞。通过Con A刺激的细胞毒性测量,T细胞功能没有缺陷。急性和慢性肝炎患者存在一种血清因子,可抑制自发和诱导的淋巴细胞细胞毒性及母细胞转化。最后,泼尼松治疗似乎抑制了CAH患者的淋巴细胞细胞毒性。