Jander S, Schroeter M, D'Urso D, Gillen C, Witte O W, Stoll G
Department of Neurology and Center for Biological and Medical Research, Heinrich-Heine-University, Düsseldorf, Germany.
Eur J Neurosci. 1998 Feb;10(2):680-8. doi: 10.1046/j.1460-9568.1998.00078.x.
Cerebral ischaemia leads to profound glial activation and leukocyte infiltration into the infarct area. In this study, we provide evidence for a dual macrophage response in focal ischaemic lesions of the rat brain. We show that a considerable proportion of macrophages in the ischaemic lesions express the CD8alphabeta heterodimer to date only described on CD8+ T cells. As known from other lesion paradigms, CD4+ macrophages were also present. Interestingly, CD8- and CD4-expressing macrophages formed two non-overlapping subpopulations. CD8+ macrophages reached their maximum during the first week with pronounced downregulation thereafter whereas CD4+ cells persisted at high levels into the second week. In contrast to cerebral ischaemia, macrophages in the spleen and in Wallerian degeneration after optic nerve axotomy expressed CD4, but not CD8. In experimental autoimmune encephalomyelitis, CD8 was mainly associated with T cells and very weakly detectable on some ramified cells resembling activated microglia. In conclusion, we show that cerebral ischaemia triggers an unusual inflammatory response characterized by the appearance of CD8+/CD4- macrophages that might exert specific functions in the pathogenesis of ischaemic brain damage.
脑缺血导致胶质细胞的强烈激活以及白细胞浸润至梗死区域。在本研究中，我们为大鼠脑局灶性缺血性损伤中的双重巨噬细胞反应提供了证据。我们发现，缺血性损伤中的相当一部分巨噬细胞表达CD8αβ异二聚体，迄今为止该异二聚体仅在CD8 + T细胞上被描述过。正如在其他损伤模型中所知，CD4 +巨噬细胞也存在。有趣的是，表达CD8和CD4的巨噬细胞形成了两个不重叠的亚群。CD8 +巨噬细胞在第一周达到峰值，此后显著下调，而CD4 +细胞在第二周仍维持在高水平。与脑缺血不同，脾脏中的巨噬细胞以及视神经轴突切断术后沃勒变性中的巨噬细胞表达CD4，但不表达CD8。在实验性自身免疫性脑脊髓炎中，CD8主要与T细胞相关，在一些类似于活化小胶质细胞的分支细胞上很难检测到。总之，我们表明脑缺血引发了一种不寻常的炎症反应，其特征是出现CD8 + / CD4 - 巨噬细胞，这些巨噬细胞可能在缺血性脑损伤的发病机制中发挥特定作用。
