Starling G C, McLellan A D, Egner W, Sorg R V, Fawcett J, Simmons D L, Hart D N
Haematology/Immunology Research Group, Christchurch Hospital, New Zealand.
Eur J Immunol. 1995 Sep;25(9):2528-32. doi: 10.1002/eji.1830250918.
Dendritic cells (DC) are potent stimulators of primary T lymphocyte responses to foreign antigen. The initial DC-T lymphocyte interaction involves the binding of the adhesion molecule leukocyte function antigen-1 (LFA-1; CD11a/CD18) on the T lymphocyte to an intercellular adhesion molecule (ICAM) on the DC. Although blood and tonsil DC express ICAM-1 (CD54) and ICAM-2 (CD102) on their surface, anti-ICAM-1 and anti-ICAM-2 monoclonal antibodies (mAb) have little inhibitory activity on the DC-stimulated mixed leukocyte reaction (MLR). We therefore examined the expression of the more recently identified LFA-1 ligand, ICAM-3 (CD50), in comparison to ICAM-1 and ICAM-2 on blood DC and sought a functional role for ICAM-3 in DC-mediated T lymphocyte responses. Resting blood DC expressed significantly more ICAM-3 than ICAM-1 or ICAM-2 as assessed by flow cytometry. Treatment of resting DC with interferon-gamma led to increased expression of ICAM-1; however, ICAM-2 and ICAM-3 levels remained relatively constant. Solid-phase recombinant chimeric molecules ICAM-1-, ICAM-2- and ICAM-3-Fc were able to co-stimulate CD4+ T lymphocyte proliferation in conjunction with suboptimal solid-phase CD3 mAb 64.1. However, the anti-ICAM-3 mAb CAL 3.10 inhibited a DC-stimulated MLR to a greater extent than anti-ICAM-1 or anti-ICAM-2 reagents and appeared to act by blocking the DC ICAM-3- T lymphocyte LFA-1 interaction. As ICAM-3 is the predominant LFA-1 ligand on resting blood DC, we postulate that DC may utilize ICAM-3 for initial DC- T lymphocyte interactions, and that ICAM-1, which is up-regulated upon DC activation, and/or ICAM-2, may contribute to DC migration or later phases of the T lymphocyte activation process.
树突状细胞（DC）是原发性T淋巴细胞对外源抗原反应的强效刺激物。最初的DC-T淋巴细胞相互作用涉及T淋巴细胞上的黏附分子白细胞功能抗原-1（LFA-1；CD11a/CD18）与DC上的细胞间黏附分子（ICAM）的结合。尽管血液和扁桃体DC在其表面表达ICAM-1（CD54）和ICAM-2（CD102），但抗ICAM-1和抗ICAM-2单克隆抗体（mAb）对DC刺激的混合淋巴细胞反应（MLR）几乎没有抑制活性。因此，我们比较了血液DC上最近发现的LFA-1配体ICAM-3（CD50）与ICAM-1和ICAM-2的表达情况，并探寻ICAM-3在DC介导的T淋巴细胞反应中的功能作用。通过流式细胞术评估，静息血液DC表达的ICAM-3明显多于ICAM-1或ICAM-2。用干扰素-γ处理静息DC会导致ICAM-1表达增加；然而，ICAM-2和ICAM-3水平保持相对恒定。固相重组嵌合分子ICAM-1-Fc、ICAM-2-Fc和ICAM-3-Fc能够与次优固相CD3 mAb 64.1共同刺激CD4 + T淋巴细胞增殖。然而，抗ICAM-3 mAb CAL 3.10对DC刺激的MLR的抑制作用比抗ICAM-1或抗ICAM-2试剂更强，并且似乎是通过阻断DC的ICAM-3-T淋巴细胞LFA-1相互作用来发挥作用。由于ICAM-3是静息血液DC上主要的LFA-1配体，我们推测DC可能利用ICAM-3进行最初的DC-T淋巴细胞相互作用，并且在DC激活后上调的ICAM-1和/或ICAM-2可能有助于DC迁移或T淋巴细胞激活过程的后期阶段。
