Crucian B, Dunne P, Friedman H, Ragsdale R, Pross S, Widen R
Department of Medical Microbiology and Immunology, College of Medicine, University of South Florida, Tampa 33612, USA.
Clin Diagn Lab Immunol. 1996 Jul;3(4):411-6. doi: 10.1128/cdli.3.4.411-416.1996.
Production of T helper 1 and T helper 2 cytokines was investigated in peripheral blood mononuclear cells (PBMCs) from multiple sclerosis (MS) patients by a newly described technique, detection of intracellular cytokines by flow cytometry in conjunction with immunophenotype analysis. T-cell gamma interferon (IFN-gamma) production and interleukin 10 (IL-10) production were examined after PBMC activation with T-cell mitogens at 5 and 24 h, and monocyte spontaneous production of IL-10 and production after PBMC activation with lipopolysaccharide (LPS) for 24 h were also examined. The data indicate that MS patients have decreased percentages of T cells capable of secreting IFN-gama compared with healthy controls, and this change is detectable at 5 and 24 h. the patients displaying decreased T-cell production of IFN-gamma were essentially confined to a group being treated with the newly approved drug Betaseron (berlex Labs, Cedar Knolls, N.J.), a recombinant form of IFN-beta (rIFN-beta 1b). By gating of the entire lymphocyte population, analysis of IFN-gama production in T cells (CD3+ versus that in non-T cells (CD3+) was possible. The percentage of IFN-gamma-producing lymphocytes that was made up of T cells was essentially unchanged between the Betaseron-treated patients, non-Betaseron-treated patients, and controls, indicating that the suppression of IFN-gamma production displayed by betaseron-treated MS patients was a nonspecific suppression of all IFN-gamma-producing lymphocytes as opposed to a suppression of T-cell production only. The data seem to indicate that treatment of MS with Betaseron corresponds to an inhibition of the lymphocyte's ability to produce IFN-gamma. No changes were detected in T-cell production of IL-10 at either time point. We also observed that MS patients in general appear to have small percentages of peripheral blood monocytes spontaneously producing slight but detectable levels of IL-10. No difference was seen regarding monocyte production of IL-10 after PBMC activation with LPS between MS patients and controls. Both populations responded with high percentages of monocytes producing IL-10. The data seem to indicate that treatment of MS with Betaseron, known to decrease the exacerbation rate of relapsing-remitting MS, corresponds to a suppression of peripheral blood lymphocyte production of IFN-gamma. Monocyte production of IL-10 may also play a role in regulating the disease process.
采用一种新描述的技术，即通过流式细胞术检测细胞内细胞因子并结合免疫表型分析，对来自多发性硬化症（MS）患者的外周血单个核细胞（PBMC）中辅助性T细胞1和辅助性T细胞2细胞因子的产生情况进行了研究。在用T细胞有丝分裂原激活PBMC后5小时和24小时，检测T细胞γ干扰素（IFN-γ）的产生以及白细胞介素10（IL-10）的产生，并且还检测了单核细胞自发产生IL-10的情况以及在用脂多糖（LPS）激活PBMC 24小时后IL-10的产生情况。数据表明，与健康对照相比，MS患者能够分泌IFN-γ的T细胞百分比降低，并且在5小时和24小时均可检测到这种变化。显示IFN-γ产生减少的患者基本上局限于一组正在接受新批准药物倍泰龙（贝林实验室，新泽西州锡达诺尔斯）治疗的患者，倍泰龙是重组形式的IFN-β（rIFN-β1b）。通过对整个淋巴细胞群体进行门控分析，可以分析T细胞（CD3 +）与非T细胞（CD3 -）中IFN-γ的产生情况。在接受倍泰龙治疗的患者、未接受倍泰龙治疗的患者和对照之间，由T细胞组成的产生IFN-γ的淋巴细胞百分比基本没有变化，这表明接受倍泰龙治疗的MS患者所表现出的IFN-γ产生抑制是对所有产生IFN-γ的淋巴细胞的非特异性抑制，而不是仅对T细胞产生的抑制。数据似乎表明，用倍泰龙治疗MS对应于抑制淋巴细胞产生IFN-γ的能力。在两个时间点均未检测到T细胞产生IL-10的变化。我们还观察到，一般而言，MS患者外周血单核细胞自发产生IL-10的比例较小，但可检测到一定水平。在MS患者和对照之间，在用LPS激活PBMC后，单核细胞产生IL-10方面未见差异。两组中产生IL-10的单核细胞百分比均很高。数据似乎表明，已知可降低复发缓解型MS恶化率的用倍泰龙治疗MS对应于抑制外周血淋巴细胞产生IFN-γ。单核细胞产生IL-10也可能在调节疾病进程中起作用。
