LYMPHOCYTES INFILTRATING THE CNS DURING INFLAMMATION DISPLAY A DISTINCTIVE PHENOTYPE AND BIND TO VCAM-1 BUT NOT TO MADCAM-1

LYMPHOCYTES INFILTRATING THE CNS DURING INFLAMMATION DISPLAY A DISTINCTIVE PHENOTYPE AND BIND TO VCAM-1 BUT NOT TO MADCAM-1
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DOI:
10.1093/intimm/7.3.481
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发表时间:
1995-03-01
影响因子:
4.4
通讯作者:
BUTCHER, EC
BUTCHER, EC
中科院分区:
医学3区
文献类型:
--
作者:
ENGELHARDT, B;CONLEY, FK;BUTCHER, EC

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被引文献

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已经在慢性炎症模型中研究了募集到CNS的炎性淋巴细胞的性质。将杀死的短小棒状杆菌注射到小鼠脑的皮质中在注射部位周围产生了限制性的炎性细胞浸润,并且可以分离募集的单核炎性细胞(IC)用于流式细胞术分析。IC的大多数是T细胞,与肠系膜淋巴结T细胞的主要幼稚群体相比,IC T细胞表达更高水平的CD 44、LFA-1和ICAM-1,以及更低水平的CD 45 RB,这些特征通常与记忆相关此外,与幼稚淋巴结T细胞的L-选择素(+)α 6-整联蛋白(低)表型相反,IC T细胞缺乏L-选择素并且是α 6-整联蛋白(-)。Mac-1,最近提出作为记忆T细胞分化的另一个标志物,没有被IC T细胞显示,表明Mac-1表达在记忆T细胞亚群中可能是异质的。肠系膜淋巴结(MLN)T细胞的亚群,可能代表经历幼稚到记忆转变的活化T细胞,但不是IC T细胞,表达高水平的α 6-、β 7-和α E-整合素,IC和MLN初始T细胞表达相当水平的α 4-整联蛋白,但IC T细胞用抗β 7 mAb和mAb DATK 32染色较差,mAb DATK 32对粘膜地址素MAdCAM-1的α 4 β 7异二聚体淋巴细胞归巢受体具有特异性,表明这些炎性细胞表达的α 4 β 1多于α 4 β 7。与此相一致,在体外粘附测定中,脑IC比MLN细胞更好地结合α 4 β 1整联蛋白配体VCAM-1和LFA-1配体ICAM-1,但与α 4 β 7配体MAdCAM-1的粘附非常差。这些发现与小鼠实验性自身免疫性脑脊髓炎中T细胞的先前免疫组织学研究相一致并扩展了该研究。并证明了存在于慢性炎症脑中的淋巴细胞的独特表型。
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-integrin(low) 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 differentation, 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.