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大鼠脑室内注射干扰素-γ后免疫反应在脑内的分布及时间调控

Distribution and temporal regulation of the immune response in the rat brain to intracerebroventricular injection of interferon-gamma.

作者信息

Peng Z C, Kristensson K, Bentivoglio M

机构信息

Institute of Anatomy and Histology, Medical Faculty, University of Verona, Italy.

出版信息

Exp Neurol. 1998 Dec;154(2):403-17. doi: 10.1006/exnr.1998.6943.

DOI:10.1006/exnr.1998.6943
PMID:9878178
Abstract

The response to intracerebroventricular administration of interferon (IFN)-gamma was examined in the adult Wistar rat brain: major histocompatibility complex (MHC) antigens class I and II, CD8 and CD4 antigens, and the macrophage/microglia antigen OX42 were analyzed in respect to saline-injected cases over 1 week. The glial cell type expressing MHC antigens was characterized with double labeling. IFN-gamma was thus found to induce MHC class I and II expression in microglia, identified by tomato lectin histochemistry, and not in GFAP-immunostained astrocytes. MHC antigen-expressing microglia was detected in the periventricular parenchyma, several fields of the cerebral cortex, cerebellum, major fiber tracts, and brainstem superficial parenchyma. Different gradients of density and staining intensity of the MHC-immunopositive elements were observed in these regions, in which MHC class I antigens persisted up to 1 week, when MHC class II induction had declined. Quantitative analysis pointed out the proliferation of OX42-immunoreactive cells in periventricular and basal brain regions. CD8+ T cells were observed in periventricular regions, basal forebrain, and fiber tracts 3 days after IFN-gamma injection and their density markedly increased by 7 days. CD4+ T cells were also seen and they were fewer than CD8+ ones. However, numerous CD4+ microglial cells were observed in periventricular and subpial regions, especially 1 week after IFN-gamma injection. Our data indicate that this proinflammatory cytokine mediates in vivo microglia activation and T cell infiltration in the brain and that the cells involved in this immune response display a regional selectivity and a different temporal regulation of antigen expression.

摘要

在成年Wistar大鼠脑中检测了脑室内注射干扰素(IFN)-γ后的反应:对注射生理盐水的大鼠在1周内分析了主要组织相容性复合体(MHC)I类和II类抗原、CD8和CD4抗原以及巨噬细胞/小胶质细胞抗原OX42。通过双重标记对表达MHC抗原的胶质细胞类型进行了特征描述。结果发现,IFN-γ可诱导经番茄凝集素组织化学鉴定的小胶质细胞表达MHC I类和II类抗原,而在GFAP免疫染色的星形胶质细胞中未诱导表达。在脑室周围实质、大脑皮质的多个区域、小脑、主要纤维束和脑干浅表实质中检测到表达MHC抗原的小胶质细胞。在这些区域观察到MHC免疫阳性成分的密度和染色强度存在不同梯度,其中MHC I类抗原可持续1周,而此时MHC II类抗原的诱导已下降。定量分析指出,OX42免疫反应性细胞在脑室周围和基底脑区增殖。IFN-γ注射3天后,在脑室周围区域、基底前脑和纤维束中观察到CD8 + T细胞,其密度在7天时显著增加。也观察到了CD4 + T细胞,其数量少于CD8 + T细胞。然而,在脑室周围和软膜下区域观察到大量CD4 +小胶质细胞,尤其是在IFN-γ注射1周后。我们的数据表明,这种促炎细胞因子在体内介导脑内小胶质细胞活化和T细胞浸润,并且参与这种免疫反应的细胞表现出区域选择性和抗原表达的不同时间调节。

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