McCombe P A, Nickson I, Tabi Z, Pender M P
Department of Medicine, University of Queensland, Royal Brisbane Hospital, Herston, Australia.
J Neuroimmunol. 1996 Nov;70(2):93-101. doi: 10.1016/s0165-5728(96)00043-4.
We have studied the effects of corticosteroid treatment on the numbers of lymphocytes obtained from the spinal cords of Lewis rats with acute experimental autoimmune encephalomyelitis (EAE) induced by inoculation with myelin basic protein (MBP) and adjuvants. Flow cytometric studies showed that treatment with dexamethasone (4 mg/kg) 8-12 h prior to study on day 14 after inoculation resulted in a reduction in the numbers of CD5+, TCR alpha beta + and V beta 8.2+ cells in the spinal cord. Limiting dilution analysis indicated that dexamethasone treatment 12 h prior to study on day 12 after inoculation reduced the frequencies of MBP-reactive and interleukin-2-responsive lymphocytes in the spinal cord to low levels, but reduced the frequency of concanavalin-A-responsive lymphocytes to a lesser extent. Using propidium iodide staining of nuclear chromatin we also studied lymphocyte apoptosis. Greater numbers of apoptotic cells were found in the cells extracted from the spinal cords of rats, examined on day 14, that had been treated 1-12 h previously with dexamethasone, than in saline-treated controls. This increased level of apoptosis was observed in the CD5+ and TCR alpha beta + cell populations. At 1-4 h after dexamethasone treatment there was a reduction in the selective apoptosis of V beta 8.2+ cells that normally occurs during spontaneous recovery from EAE. Therefore apoptosis of V beta 8.2+ cells cannot explain the reduction in the numbers of V beta 8.2+ cells and MBP-reactive cells in the CNS after dexamethasone treatment. By 8-12 h after dexamethasone treatment the selectivity of the apoptotic process was restored. These studies suggest that a reduction in the number of T-lymphocytes in the central nervous system contributes to the beneficial effects of corticosteroids in EAE.
我们研究了皮质类固醇治疗对从接种髓鞘碱性蛋白（MBP）和佐剂诱导的急性实验性自身免疫性脑脊髓炎（EAE）的Lewis大鼠脊髓中获取的淋巴细胞数量的影响。流式细胞术研究表明，在接种后第14天研究前8 - 12小时用地塞米松（4mg/kg）治疗，导致脊髓中CD5 +、TCRαβ +和Vβ8.2 +细胞数量减少。极限稀释分析表明，在接种后第12天研究前12小时用地塞米松治疗，可将脊髓中MBP反应性和白细胞介素-2反应性淋巴细胞的频率降低至低水平，但对伴刀豆球蛋白A反应性淋巴细胞频率的降低程度较小。我们还使用碘化丙啶对核染色质进行染色来研究淋巴细胞凋亡。在接种后第14天检查的、先前1 - 12小时用地塞米松治疗的大鼠脊髓中提取的细胞中，发现凋亡细胞的数量比生理盐水处理的对照组更多。在CD5 +和TCRαβ +细胞群体中观察到这种凋亡水平的增加。在地塞米松治疗后1 - 4小时，EAE自发恢复过程中正常发生的Vβ8.2 +细胞的选择性凋亡减少。因此，Vβ8.2 +细胞的凋亡不能解释地塞米松治疗后中枢神经系统中Vβ8.2 +细胞和MBP反应性细胞数量的减少。在地塞米松治疗后8 - 12小时，凋亡过程的选择性得以恢复。这些研究表明，中枢神经系统中T淋巴细胞数量的减少有助于皮质类固醇对EAE的有益作用。
