Investigation on receptor systems mediating lymphocyte recirculation

为了确定参与淋巴细胞再循环的分子，特别是淋巴细胞与高内皮细胞之间的相互作用，我们尝试建立了大鼠高内皮小静脉(HEV)来源的培养细胞系。然后，我们开发了一种体外实验，用来定量淋巴细胞与HE细胞的相互作用，这是淋巴细胞再循环中最重要的过程。我们曾多次尝试制备能够阻断这种异种细胞相互作用的单抗，并随后获得了两种单抗，其中一种识别大鼠ICAM-1，另一种识别大鼠LFA-1。通过上述体外实验，我们研究了LFA-1和ICAM-1分子在淋巴细胞-HEV相互作用中的作用程度。我们已经证明：(1)LFA-1和ICAM-1在静息淋巴细胞与HEV的相互作用中都不起作用；(2)当淋巴细胞被激活时，依赖于LFA-1的黏附通路开始发挥作用，尽管依赖ICAM-1的黏附通路在淋巴细胞与HE细胞之间的相互作用中被不同地使用，但取决于激活的程度。正在进行进一步的尝试，以确定直接参与淋巴细胞-HE细胞相互作用的分子。

In order to identify molecules involved in lymphocyte recirculation, particularly interactions between lymphocytes and HE (high endothelial) cells, we tried successfully to establish cultured cell lines derived from rat high endothelial venules (HEV). We then developed an in vitro assay with which to quantitate lymphocyte interaction with HE cells, a most important process in lymphocyte recirculation. We have made number of attempts to generate monoclonal antibodies (MAb) which can block this heterocellular interaction, and have subsequently obtained two MAb, one of which recognizes the rat ICAM-1, the other the rat LFA-1. By the use of the in vitro assay described above, we investigated the extent of contribution of the LFA-1 and ICAM-1 molecules in lymphocyte-HEV interaction. We have demonstrated that; (1) neither LFA-1 nor ICAM-1 plays a significant role in interaction between resting lymphocytes and HEV, (2) when lymphocytes are activated, LFA-1 dependent adhesion pathways becomes operative, although, depending on the extent of activation, ICAM- 1 dependent adhesion pathway is differentially used in the interaction between lymphocytes and HE cells. Further attempts are being made to identify molecules directly involved in lymphocyte-HE cell interaction.