Lindor K D, Wiesner R H, Dickson E R, Homburger H A
Department of Medicine, Mayo Clinic, Rochester, Minnesota 55905.
Hepatology. 1988 Nov-Dec;8(6):1555-9. doi: 10.1002/hep.1840080614.
Blastogenesis of autoreactive T lymphocytes in the autologous mixed lymphocyte reaction has been shown to be decreased in patients with primary biliary cirrhosis, but the mechanisms underlying this abnormality are not known. To investigate further the abnormal autologous mixed lymphocyte reaction in primary biliary cirrhosis, we measured the activation of autoreactive helper/inducer and suppressor/cytotoxic T lymphocytes concurrently with blastogenesis in 35 patients with primary biliary cirrhosis and 18 healthy controls. Blastogenesis was diminished in autologous mixed lymphocyte reaction cultures from primary biliary cirrhosis patients compared to the control subjects (25,273 +/- 20,259 dpm vs. 36,004 +/- 14,951 dpm, p less than 0.02), but cultures from patients with primary biliary cirrhosis contained significantly increased percentages of activated helper/inducer and suppressor/cytotoxic T lymphocytes: 20.6 +/- 7.9 vs. 15.5 +/- 5.3%, p less than 0.008, and 9.8 +/- 7.8 vs. 5.4 +/- 3.0%, p less than 0.02, respectively. These findings were not related to the histologic stage of liver disease or to the serum bilirubin concentration and were not associated with abnormalities of lymphocyte subsets in fresh peripheral blood specimens. We conclude that the percentage of autoreactive T lymphocytes in autologous mixed lymphocyte reaction cultures from peripheral blood is increased in patients with primary biliary cirrhosis and diminished blastogenesis in autologous mixed lymphocyte reaction cultures is not due to the loss of autoreactive T lymphocytes from peripheral blood. Diminished blastogenesis reflects a diminished proliferative response of activated, autoreactive T lymphocytes in primary biliary cirrhosis. Possible mechanisms that may account for the paradoxical findings of decreased blastogenesis and increased activation of autoreactive T lymphocytes in primary biliary cirrhosis are discussed.(ABSTRACT TRUNCATED AT 250 WORDS)
原发性胆汁性肝硬化患者自体混合淋巴细胞反应中自身反应性T淋巴细胞的母细胞化已被证明有所降低，但其异常背后的机制尚不清楚。为了进一步研究原发性胆汁性肝硬化中异常的自体混合淋巴细胞反应，我们在35例原发性胆汁性肝硬化患者和18名健康对照者中，同时测量了自身反应性辅助/诱导性和抑制/细胞毒性T淋巴细胞的活化情况以及母细胞化程度。与对照受试者相比，原发性胆汁性肝硬化患者的自体混合淋巴细胞反应培养物中的母细胞化减少（25,273±20,259 dpm对36,004±14,951 dpm，p<0.02），但原发性胆汁性肝硬化患者的培养物中活化的辅助/诱导性和抑制/细胞毒性T淋巴细胞的百分比显著增加：分别为20.6±7.9%对15.5±5.3%，p<0.008，以及9.8±7.8%对5.4±3.0%，p<0.02。这些发现与肝病的组织学阶段或血清胆红素浓度无关，也与新鲜外周血标本中淋巴细胞亚群的异常无关。我们得出结论，原发性胆汁性肝硬化患者外周血自体混合淋巴细胞反应培养物中自身反应性T淋巴细胞的百分比增加，且自体混合淋巴细胞反应培养物中母细胞化减少并非由于外周血中自身反应性T淋巴细胞的丢失。母细胞化减少反映了原发性胆汁性肝硬化中活化的自身反应性T淋巴细胞增殖反应的减弱。文中讨论了可能解释原发性胆汁性肝硬化中母细胞化减少和自身反应性T淋巴细胞活化增加这一矛盾发现的机制。（摘要截短于250字）
