Tietz W, Hamann A
Department of Immunology, University Hospital, Eppendorf, Hamburg, Germany.
Eur J Immunol. 1997 Sep;27(9):2225-32. doi: 10.1002/eji.1830270916.
Lymphocyte differentiation is connected with profound alterations in the migratory pattern of lymphocytes. Whereas naive cells predominantly recirculate through lymphoid tissues, activated lymphocytes acquire an increased preference for immigration into non-lymphoid tissues and a reduced capacity for recirculation via high endothelial venules (HEV). A variety of data had indicated that memory-related subpopulations of cells in man and sheep, classified by the low expression of the CD45RA isotype, also lack the capacity to recirculate via HEV. However, recent data in the rat called these results into question. We therefore analyzed the migration properties of murine CD4+ T cell subpopulations defined by several markers used to distinguish memory from naive CD4+ cells in mice, namely CD45RB, L-selectin and CD44. Our data clearly show that the majority of putative memory cells expressing either low levels of CD45RB, low levels of L-selectin or high levels of CD44 display a strongly reduced capacity for direct entry into lymphoid tissues, including the spleen, from the blood stream. The accumulation in peripheral lymph nodes is further reduced by treatment with anti-L-selectin antibody, which blocks their entry via HEV. This indicates that memory CD4+ T cells are not excluded from crossing lymph node HEV, and that the numbers of cells entering the node via this route exceed the numbers entering via the afferent lymph, at least in the absence of local inflammation. Concomitantly, a strongly enhanced localization of cells of the memory phenotype is observed in lung and liver as compared with naive cells. Trafficking to specific sites such as skin or gut mucosa is not a prominent feature of the total population of memory cells. The trafficking to lung and liver and an increased ability to bind to dendritic cells, demonstrable in in vitro adhesion assays, suggest a more sessile phenotype of most memory cells. With respect to these properties, memory cells have a surprizing similarity to fully activated lymphocytes.
淋巴细胞分化与淋巴细胞迁移模式的深刻改变相关。未活化细胞主要通过淋巴组织再循环，而活化的淋巴细胞更倾向于迁移至非淋巴组织，且经高内皮微静脉（HEV）再循环的能力降低。多种数据表明，人和绵羊中根据CD45RA同种型低表达分类的与记忆相关的细胞亚群也缺乏经HEV再循环的能力。然而，大鼠的最新数据对这些结果提出了质疑。因此，我们分析了小鼠CD4 + T细胞亚群的迁移特性，这些亚群由用于区分小鼠记忆性和未活化CD4 +细胞的几种标志物定义，即CD45RB、L-选择素和CD44。我们的数据清楚地表明，大多数表达低水平CD45RB、低水平L-选择素或高水平CD / 44的假定记忆细胞从血流直接进入包括脾脏在内的淋巴组织的能力大大降低。用抗L-选择素抗体处理可进一步减少外周淋巴结中的细胞积聚，该抗体可阻断它们经HEV进入。这表明记忆性CD4 + T细胞不被排除穿过淋巴结HEV，并且至少在没有局部炎症的情况下，经此途径进入淋巴结的细胞数量超过经输入淋巴管进入的细胞数量。与此同时，与未活化细胞相比，在肺和肝脏中观察到记忆表型细胞的定位明显增强。向皮肤或肠道黏膜等特定部位的迁移不是记忆细胞总数的突出特征。在体外黏附试验中可证明，向肺和肝脏的迁移以及与树突状细胞结合能力的增强表明大多数记忆细胞具有更固定的表型。就这些特性而言，记忆细胞与完全活化的淋巴细胞有惊人的相似性。
