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HLA class II molecules (HLA-DR -DP -DQ) on cells in the human CNS studied in situ and in vitro.

机译:原位和体外研究人类CNS细胞上的HLA II类分子(HLA-DR-DP-DQ)。

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摘要

Human leucocyte antigen (HLA) class II molecules expressed by antigen-presenting cells (APC) are major restriction elements in the interaction between APC and T cells of the CD4+ subtype. To explore the immune accessory function of cells in the central nervous system (CNS), we studied the expression of HLA-DR, -DP, and -DQ molecules on CNS cells in situ and in vitro. Reactive microglia and perivascular cells in multiple sclerosis lesions expressed all three HLA class II molecules, whereas microglia in the normal CNS expressed HLA-DR only. All three HLA class II molecules were up-regulated on cultured microglia after stimulation with interferon-gamma (IFN-gamma). Microglial stimulation of allogeneic CD4+ T cells in a mixed lymphocyte reaction (MLR) was effectively blocked using anti-HLA-DR monoclonal antibodies (mAb) but not using anti-HLA-DQ mAb. HLA class II-positive astrocytes and endothelial cells were not identified in normal or diseased CNS. Cultured astrocytes stimulated with IFN-gamma could, however, be induced to express HLA class II antigens of all subtypes, although great variability was observed between different donors. Our results indicate that although both microglia and astrocytes are capable of expressing all HLA class II subtypes in vitro, subtype expression differs between normal and pathological states in situ. Such selective expression may be associated with functional properties.
机译:由抗原呈递细胞(APC)表达的人类白细胞抗原(HLA)II类分子是APC与CD4 +亚型的T细胞之间相互作用的主要限制因素。为了探索中枢神经系统(CNS)中细胞的免疫辅助功能,我们研究了HLA-DR,-DP和-DQ分子在CNS细胞上的原位和体外表达。多发性硬化病灶中的反应性小胶质细胞和血管周细胞表达所有三种HLA II类分子,而正常CNS中的小胶质细胞仅表达HLA-DR。干扰素-γ(IFN-γ)刺激后,培养的小胶质细胞上所有三种HLA II类分子均上调。使用抗HLA-DR单克隆抗体(mAb)可以有效地阻止混合淋巴细胞反应(MLR)中同种异体CD4 + T细胞的小胶质细胞刺激作用,而不能使用抗HLA-DQ mAb来有效阻断。在正常或患病的中枢神经系统中未鉴定出HLA II类阳性星形胶质细胞和内皮细胞。尽管在不同的供体之间观察到很大的变异性,但是可以诱导用IFN-γ刺激的培养的星形胶质细胞表达所有亚型的HLA II类抗原。我们的结果表明,尽管小胶质细胞和星形胶质细胞都能够在体外表达所有HLA II类亚型,但是在正常状态和病理状态下,亚型表达有所不同。这种选择性表达可以与功能特性相关。

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