Keystone E C, Poplonski L, Snow K M, Martell M
Rheumatic Disease Unit, Wellesley Hospital and Ontario Cancer Institute, University of Toronto, Canada.
Clin Exp Immunol. 1989 Nov;78(2):184-8.
We examined AMLR reactivity of unseparated T cells and CD4+ and CD8+ T cell subsets in peripheral blood from 11 rheumatoid arthritis (RA) patients and 10 healthy controls. T cell subsets were isolated by negative selection using complement mediated cytotoxicity. AMLR reactivity of six patients (designated RA-L was reduced below the range of the controls' responses. Five patients (designated RA-N) exhibited normal AMLR reactivity. We observed impaired AMLR reactivity of CD4+ T cells from RA-L relative to RA-N and healthy controls (P < 0.05). CD4+ T cell reactivity of RA-L was reconstituted to normal with pharmacological doses of recombinant interleukin-2 (IL-2) (100 U/ml). In contrast, CD8+ T cells from RA-L in the presence of 100 U/ml IL-2 exhibited markedly impaired AMLR reactivity relative to RA-N and healthy controls (P < 0.05). Dose-response studies revealed partial reconstitution of CD4 T cells with physiological concentrations of IL-2 (10 U/ml). To examine the possibility that in vivo pre-activation of T cells in RA accounted for the findings, T cells or subsets were cultured alone for 7 days in the presence of 100 U/ml IL-2. A trend toward enhanced reactivity of CD4+ and CD8+ T cells in L-RA relative to N-RA and healthy controls was observed, but the differences were not statistically significant. There was no correlation between reactivity of T cells alone in the presence of IL-2 and AMLR reactivity. The results suggest the possibility that abnormal AMLR reactivity of CD4+ and CD8+ T cell subsets in RA may arise as a consequence of different pathophysiological mechanisms.
我们检测了11例类风湿关节炎（RA）患者和10名健康对照者外周血中未分离的T细胞以及CD4⁺和CD8⁺ T细胞亚群的自体混合淋巴细胞反应（AMLR）。使用补体介导的细胞毒性通过阴性选择分离T细胞亚群。6例患者（称为RA-L）的AMLR反应性降低至低于对照组反应范围。5例患者（称为RA-N）表现出正常的AMLR反应性。我们观察到相对于RA-N和健康对照，RA-L患者的CD4⁺ T细胞的AMLR反应性受损（P < 0.05）。用药理剂量的重组白细胞介素-2（IL-2）（100 U/ml）可使RA-L患者的CD4⁺ T细胞反应性恢复正常。相比之下，在存在100 U/ml IL-2的情况下，RA-L患者的CD8⁺ T细胞相对于RA-N和健康对照表现出明显受损的AMLR反应性（P < 0.05）。剂量反应研究显示生理浓度的IL-2（10 U/ml）可部分恢复CD4 T细胞。为了研究RA中T细胞体内预激活是否能解释这些发现，将T细胞或亚群在100 U/ml IL-2存在的情况下单独培养7天。观察到相对于N-RA和健康对照，L-RA患者的CD4⁺和CD8⁺ T细胞反应性有增强趋势，但差异无统计学意义。在IL-2存在的情况下单独T细胞的反应性与AMLR反应性之间无相关性。结果提示RA中CD4⁺和CD8⁺ T细胞亚群异常的AMLR反应性可能是由不同病理生理机制导致的。
