Prickett T C, McKenzie J L, Hart D N
Department of Haematology, Christchurch Hospital, New Zealand.
Transplantation. 1992 Feb;53(2):483-90. doi: 10.1097/00007890-199202010-00041.
Dendritic cells are specialist antigen-presenting cells that have a unique ability to stimulate a primary T cell response. Activation of T cells by DC depends on the formation of cell clusters creating DC-T cell membrane contact that probably involves adhesion molecules. Monoclonal antibodies were used to study adhesion molecules on DC, including members of the integrin and immunoglobulin supergene families. DC expressed LFA-1, ICAM-1, LFA-3, and the Hermes antigen, but no other integrin or immunoglobulin supergene family adhesion molecules were detected using a sensitive immunoperoxidase staining technique. Monoclonal antibodies to LFA-1 alpha and LFA-1 beta inhibited DC-stimulated allogeneic T cell (MLR) responses by 75 +/- 12% and 74 +/- 8%, respectively, as did the anti-LFA-3 (56 +/- 3% inhibition) and anti-LFA-2 (60 +/- 5% inhibition) antibodies. Three different anti-ICAM-1 antibodies inhibited only to a limited degree (mean range 8-24%). The inhibitory effect of the LFA-1 and LFA-3 antibodies was maximal if added early to the MLR. The inhibitory effect of the different antibodies was associated with variable decreases in DC-T cell cluster stability. The simultaneous addition of monoclonal antibodies to MLRs and preincubation washing experiments established that DC have at least 3 independent adhesion ligand interactions (LFA-1-ICAM-1, ICAM-1-LFA-1, and LFA-3-CD2) with T cells. It seems likely that the additional ligand for LFA-1, ICAM-2, is expressed on DC and contributes significantly to DC-T cell adherence and T cell activation. The membrane mobility of these molecules may also be important in the DC-T cell activation process.
树突状细胞是专门的抗原呈递细胞,具有刺激初始T细胞反应的独特能力。树突状细胞对T细胞的激活取决于细胞簇的形成,这种细胞簇会形成树突状细胞与T细胞膜的接触,这可能涉及黏附分子。单克隆抗体被用于研究树突状细胞上的黏附分子,包括整合素和免疫球蛋白超基因家族的成员。树突状细胞表达淋巴细胞功能相关抗原-1(LFA-1)、细胞间黏附分子-1(ICAM-1)、淋巴细胞功能相关抗原-3(LFA-3)和Hermes抗原,但使用灵敏的免疫过氧化物酶染色技术未检测到其他整合素或免疫球蛋白超基因家族的黏附分子。抗LFA-1α和抗LFA-1β单克隆抗体分别抑制树突状细胞刺激的同种异体T细胞(混合淋巴细胞反应,MLR)反应75±12%和74±8%,抗LFA-3(抑制率56±3%)和抗LFA-2(抑制率60±5%)抗体也有类似效果。三种不同的抗ICAM-1抗体仅产生有限程度的抑制(平均抑制范围为8 - 24%)。如果在混合淋巴细胞反应早期添加LFA-1和LFA-3抗体,其抑制作用最大。不同抗体的抑制作用与树突状细胞 - T细胞簇稳定性的不同程度降低相关。将单克隆抗体同时添加到混合淋巴细胞反应中以及预孵育洗涤实验表明,树突状细胞与T细胞至少有3种独立的黏附配体相互作用(LFA-1 - ICAM-1、ICAM-1 - LFA-1和LFA-3 - CD2)。看起来LFA-1的额外配体ICAM-2可能在树突状细胞上表达,并对树突状细胞 - T细胞黏附和T细胞激活有显著贡献。这些分子的膜流动性在树突状细胞 - T细胞激活过程中可能也很重要。