Engelhardt B, Conley F K, Kilshaw P J, Butcher E C
Department of Pathology, Stanford University School of Medicine, CA 94305, USA.
Int Immunol. 1995 Mar;7(3):481-91. doi: 10.1093/intimm/7.3.481.
The nature of inflammatory lymphocytes recruited to the CNS has been studied in a model of chronic inflammation. Injection of killed Corynebacterium parvum into the cortex of the mouse brain produces a circumscribed inflammatory cellular infiltrate around the injection site, and recruited mononuclear inflammatory cells (IC) can be isolated for flow cytometric analysis. The majority of IC were T cells. In comparison with the predominant naive population of mesenteric lymph node T cells, IC T cells express much higher levels of CD44, LFA-1 and ICAM-1, and lower levels of CD45RB, features commonly associated with memory (previously activated) cells. In addition, in contrast to the L-selectin+ alpha 6-integrinlow phenotype of naive lymph node T cells, IC T cells lacked L-selectin and were alpha 6-integrin-. Mac-1, recently proposed as another marker of memory T cell differentiation, was not displayed by IC T cells, suggesting that Mac-1 expression may be heterogeneous among memory T cell subsets. A subset of mesenteric lymph node (MLN) T cells, probably representing activated T cells undergoing the naive to memory transition, but not of IC T cells, expressed high levels of alpha 6-, beta 7- and alpha E-integrin. IC and MLN naive T cells expressed comparable levels of alpha 4-integrin, but IC T cells stain poorly with anti-beta 7 mAbs and with mAb DATK 32, specific for the alpha 4 beta 7 heterodimeric lymphocyte homing receptor for the mucosal addressin MAdCAM-1, suggesting that these inflammatory cells express more alpha 4 beta 1 than alpha 4 beta 7. Consistent with this, in in vitro adhesion assays, brain IC bound better than MLN cells to the alpha 4 beta 1 integrin ligand VCAM-1 and the LFA-1 ligand ICAM-1 but adhered very poorly to the alpha 4 beta 7 ligand MAdCAM-1. These findings are consistent with and extend previous immunohistological studies of T cells in murine experimental autoimmune encephalomyelitis, and demonstrate a distinctive phenotype for lymphocytes being present in the chronically inflamed brain.
在慢性炎症模型中，对募集到中枢神经系统的炎性淋巴细胞的性质进行了研究。将灭活的细小棒状杆菌注射到小鼠脑皮质中，在注射部位周围会产生局限性炎性细胞浸润，并且可以分离出募集的单核炎性细胞（IC）用于流式细胞术分析。大多数IC是T细胞。与肠系膜淋巴结T细胞中占主导地位的初始群体相比，IC T细胞表达更高水平的CD44、LFA-1和ICAM-1，以及更低水平的CD45RB，这些特征通常与记忆（先前活化的）细胞相关。此外，与初始淋巴结T细胞的L-选择素⁺α6-整合素低表型相反，IC T细胞缺乏L-选择素且为α6-整合素阴性。最近被提议作为记忆T细胞分化的另一个标志物的Mac-1，IC T细胞并未显示，这表明Mac-1表达在记忆T细胞亚群中可能是异质性的。肠系膜淋巴结（MLN）T细胞的一个亚群，可能代表正在经历从初始到记忆转变的活化T细胞，但IC T细胞不表达，该亚群表达高水平的α6-、β7-和αE-整合素。IC和MLN初始T细胞表达相当水平的α4-整合素，但IC T细胞用抗β7单克隆抗体和对黏膜地址素MAdCAM-1的α4β7异二聚体淋巴细胞归巢受体具有特异性的单克隆抗体DATK 32染色效果较差，这表明这些炎性细胞表达的α4β1比α4β7更多。与此一致的是，在体外黏附试验中，脑IC与α4β1整合素配体VCAM-1和LFA-1配体ICAM-1的结合优于MLN细胞，但与α4β7配体MAdCAM-1的黏附非常差。这些发现与之前对小鼠实验性自身免疫性脑脊髓炎中T细胞的免疫组织学研究一致并有所扩展，并且证明了存在于慢性炎症脑内的淋巴细胞具有独特的表型。
