Ransohoff R M, Tuohy V K, Barna B P, Rudick R A
Department of Molecular Biology, Cleveland Clinic Foundation, OH.
J Neuroimmunol. 1992 Apr;37(3):169-76. doi: 10.1016/0165-5728(92)90001-2.
HLA-DR expression on circulating monocytes varies as a function of disease activity in patients with multiple sclerosis (MS), a putative immunopathological demyelinating disorder. Specifically, monocytes isolated from subjects with active MS exhibit reduced HLA-DR antigen density, and immunoregulatory aberrations such as impaired T lymphocyte-mediated suppression correlate strongly with this quantitative defect. To address the mechanism underlying this phenomenon, we compared in vitro regulation of HLA-DR by interferon beta (IFN beta), interferon gamma (IFN gamma), and lipopolysaccharide (LPS) in monocytes from patients with stable and active MS and normal individuals. Interferon-gamma and LPS enhanced monocyte expression of HLA-DR equally in both MS patient groups, suggesting that underexpression of HLA-DR in active MS was not explained by impaired in vivo monocyte responsiveness. Furthermore, interferon regulation of HLA-DR in normals and stable MS subjects was indistinguishable, indicating that aberrant interferon-mediated regulation of class II major histocompatibility complex (MHC) on circulating monocytes does not appear to be a characteristic of the MS disease state.
在多发性硬化症（MS）患者中，循环单核细胞上的HLA - DR表达随疾病活动而变化，MS是一种假定的免疫病理脱髓鞘疾病。具体而言，从患有活动性MS的受试者中分离出的单核细胞表现出HLA - DR抗原密度降低，并且免疫调节异常，如T淋巴细胞介导的抑制受损，与这种定量缺陷密切相关。为了探究这一现象背后的机制，我们比较了干扰素β（IFNβ）、干扰素γ（IFNγ）和脂多糖（LPS）对稳定期和活动期MS患者以及正常个体单核细胞中HLA - DR的体外调节作用。在两个MS患者组中，干扰素γ和LPS均同等程度地增强了单核细胞HLA - DR的表达，这表明活动性MS中HLA - DR的低表达不能用体内单核细胞反应性受损来解释。此外，正常人和稳定期MS受试者中HLA - DR的干扰素调节作用没有差异，这表明循环单核细胞上II类主要组织相容性复合体（MHC）的干扰素介导调节异常似乎不是MS疾病状态的特征。
