Zhou Y W, Komada Y, Inaba H, Deguchi T, Sugiyama K, Azuma E, Sakurai M
Department of Pediatrics, Mie University School of Medicine, Tsu, Japan.
Immunol Invest. 1998 Jul-Sep;27(4-5):309-22. doi: 10.3109/08820139809070904.
We investigated the functional significance of the adhesion molecules CD2 and lymphocyte function-associated antigen-1 (LFA-1: CD11a/CD18) in Fas-Fas ligand (FasL) death pathway. Interleukin-2-activated T cells expressed a large amount of FasL protein and could efficiently kill a Fas-sensitive leukemic cell line, MML-1. The major part (over 80%) of MML-1 cell death was Fas-dependent. Antibodies to CD2 and CD11a/CD18 completely inhibited MML-1 target cell lysis, whereas effector to target cell binding was partially reduced or not affected at all. These results suggest that effector/target interaction via CD2/CD58 and LFA-1/CD54 systems would be essential for triggering target cell death. More interestingly, there is the discordance in the ability of anti-CD2, and particularly anti-LFA-1 antibodies, to block Fas-dependent cell death versus effector to target conjugate formation. This suggests some non-adhesive role for CD2 and LFA-1 in induction of Fas-dependent cell death. Although these antibodies were capable of inhibiting T cell proliferative response, there was no significant reduction of FasL or granzyme B expression. Thus, the signaling pathway for growth inhibition via CD2 and LFA-1 could not be linked to signaling for FasL and granzyme B expression.
我们研究了黏附分子CD2和淋巴细胞功能相关抗原-1（LFA-1：CD11a/CD18）在Fas-Fas配体（FasL）死亡途径中的功能意义。白细胞介素-2激活的T细胞表达大量FasL蛋白，并能有效杀伤Fas敏感的白血病细胞系MML-1。MML-1细胞死亡的主要部分（超过80%）是Fas依赖性的。抗CD2和CD11a/CD18抗体完全抑制MML-1靶细胞裂解，而效应细胞与靶细胞的结合仅部分减少或完全不受影响。这些结果表明，通过CD2/CD58和LFA-1/CD54系统的效应细胞/靶细胞相互作用对于触发靶细胞死亡至关重要。更有趣的是，抗CD2，尤其是抗LFA-1抗体，在阻断Fas依赖性细胞死亡与效应细胞与靶细胞共轭形成的能力上存在不一致。这表明CD2和LFA-1在诱导Fas依赖性细胞死亡中具有一些非黏附作用。尽管这些抗体能够抑制T细胞增殖反应，但FasL或颗粒酶B的表达没有显著降低。因此，通过CD2和LFA-1抑制生长的信号通路与FasL和颗粒酶B表达的信号通路无关。
