Zeine R, Owens T
Department of Medicine, Montreal Neurological Institute, McGill University, Quebec, Canada.
J Neuroimmunol. 1992 Sep;40(1):57-69. doi: 10.1016/0165-5728(92)90213-5.
In experimental allergic encephalomyelitis (EAE), autoimmune T cells infiltrate the central nervous system (CNS) and initiate demyelinating pathology. We have used flow cytometry to directly analyse the migration to the CNS of MBP-reactive CD4+ T cells labelled with a lipophilic fluorescent dye (PKH2), in SJL/J mice with passively transferred EAE. Labelled cells constituted about 45% of the CNS CD4+ population at the time of EAE onset. Almost all (greater than 90%) of the PKH2-labelled CD4+ T cells from EAE CNS were blasts and were alpha/beta T cell receptor (TCR)+, CD44(Pgp-1)high, and the majority were CD45RB(low). By contrast, most PKH2-labelled CD4+ T cells in lymph nodes, although CD44high, were CD45RBhigh cells. The cells that were transferred to induce EAE were essentially similar to antigen-primed lymph node cell populations, containing less than 15% CD44high cells, and most of them were CD45RBhigh. The CD44high CD45RB(low) phenotype is characteristic of memory/effector T cells that have been activated by antigen recognition. The difference in CD45RB expression between CNS and LN could therefore reflect differential exposure and/or response to antigen. Consistent with this, PKH2-labelled CD4+ cells isolated from the CNS were responsive to MBP in vitro, whereas PKH2+ CD4+ cells from lymph nodes showed almost undetectable responses. In control experiments in which ovalbumin (OVA)-reactive T cells were transferred, a small number of fluorescent-labelled CD4+ T cells were also detected in CNS, but there were very few blasts, and these remained CD45RBhigh. These results argue for induction of the memory/effector phenotype of CD4+ T cells, and their selective retention in the CNS, as a consequence of antigen recognition.
在实验性变应性脑脊髓炎（EAE）中，自身免疫性T细胞浸润中枢神经系统（CNS）并引发脱髓鞘病变。我们运用流式细胞术，直接分析了在被动转移EAE的SJL/J小鼠中，用亲脂性荧光染料（PKH2）标记的髓鞘碱性蛋白（MBP）反应性CD4⁺ T细胞向CNS的迁移情况。在EAE发病时，标记细胞约占CNS中CD4⁺细胞群体的45%。几乎所有（超过90%）来自EAE中枢神经系统的PKH2标记的CD4⁺ T细胞都是母细胞，且为α/β T细胞受体（TCR）⁺、CD44（Pgp-1）高表达，大多数为CD45RB低表达。相比之下，淋巴结中大多数PKH2标记的CD4⁺ T细胞尽管CD44高表达，但却是CD45RB高表达细胞。用于诱导EAE的转移细胞本质上与抗原致敏的淋巴结细胞群体相似，CD44高表达细胞少于15%，且大多数为CD45RB高表达。CD44高表达CD45RB低表达表型是经抗原识别激活的记忆/效应T细胞的特征。因此，中枢神经系统和淋巴结之间CD45RB表达的差异可能反映了对抗原的不同暴露和/或反应。与此一致的是，从CNS分离的PKH2标记的CD4⁺细胞在体外对MBP有反应，而来自淋巴结的PKH2⁺ CD4⁺细胞几乎检测不到反应。在转移卵清蛋白（OVA）反应性T细胞的对照实验中，在中枢神经系统中也检测到少量荧光标记的CD4⁺ T细胞，但母细胞很少，且这些细胞仍为CD45RB高表达。这些结果表明，作为抗原识别的结果，CD4⁺ T细胞的记忆/效应表型被诱导，并在中枢神经系统中选择性保留。
