Hauss P, Selz F, Cavazzana-Calvo M, Fischer A
INSERM U429, Hôpital Necker-Enfants Malades, Paris, France.
Eur J Immunol. 1995 Aug;25(8):2285-94. doi: 10.1002/eji.1830250826.
Dendritic cells (DC) are the main antigen-presenting cells for the initiation of primary T cell-mediated immune responses. In the first stage of activation, T cells bind to DC in an antigen-independent manner. We studied the adhesion characteristics of human CD4+ T cells to DC generated from CD34+ hematopoietic progenitors following 12 to 13 days of culture in the presence of granulocyte/macrophage colony-stimulating factor and tumor necrosis factor-alpha. A majority of these cells had the morphology, phenotype and functions of DC. CD4+ T/DC adhesion was measured by means of fluorescence microscopy and flow cytometry. Four independent receptor/ligand pathways, LFA-1/ICAM, ICAM/LFA-1, CD2/LFA-3 and CD28/CD80, were involved in the transient adhesion of DC to CD4+ T cells in antigen-independent and specific alloantigen-dependent situations, as shown by blocking experiments using monoclonal antibodies. The antibodies also blocked a primary mixed lymphocyte reaction (MLR) in which DC were used as stimulatory cells. Adhesion of alloreactive CD4+ T cells to antigen-presenting DC was stronger than that of resting CD4+ T cells, while peak adhesion occurred after 5 and 20 min, respectively. The LFA-1 ligands involved in adhesion of resting CD4 T cells to DC and alloreactive CD4+ T cells to specific DC differed in part, since ICAM-3 on resting T cells and ICAM-1 on alloreactive T lymphocytes preferentially bound LFA-1. Studies of interactions between DC and phorbol ester-activated T cells expressing the CD40 ligand revealed a fifth independent adhesion pathway, CD40/CD40 ligand. CD4-mediated regulation of CD4+ T/DC adhesion was suggested by the observation that preincubation of CD4+ T cells and DC individually with anti-CD4 antibodies inhibited adhesion. In addition, antibodies specific for HLA class II molecules inhibited adhesion when used to pretreat DC but not alloactivated CD4+ T cells.
树突状细胞（DC）是启动原发性T细胞介导的免疫反应的主要抗原呈递细胞。在激活的第一阶段，T细胞以抗原非依赖的方式与DC结合。我们研究了在粒细胞/巨噬细胞集落刺激因子和肿瘤坏死因子-α存在的情况下，培养12至13天后，人CD4 + T细胞与由CD34 +造血祖细胞产生的DC的粘附特性。这些细胞中的大多数具有DC的形态、表型和功能。通过荧光显微镜和流式细胞术测量CD4 + T/DC粘附。如使用单克隆抗体的阻断实验所示，四种独立的受体/配体途径，即淋巴细胞功能相关抗原-1（LFA-1）/细胞间粘附分子（ICAM）、ICAM/LFA-1、CD2/LFA-3和CD28/CD80，参与了DC在抗原非依赖和特异性同种异体抗原依赖情况下与CD4 + T细胞的短暂粘附。这些抗体还阻断了以DC作为刺激细胞的原发性混合淋巴细胞反应（MLR）。同种反应性CD4 + T细胞与抗原呈递DC的粘附比静止CD4 + T细胞更强，而峰值粘附分别在5分钟和20分钟后出现。静止CD4 T细胞与DC以及同种反应性CD4 + T细胞与特异性DC粘附所涉及的LFA-1配体部分不同，因为静止T细胞上的ICAM-3和同种反应性T淋巴细胞上的ICAM-1优先结合LFA-1。对DC与表达CD40配体的佛波酯激活的T细胞之间相互作用的研究揭示了第五条独立的粘附途径，即CD40/CD40配体。CD4 + T细胞和DC分别与抗CD4抗体预孵育可抑制粘附，这一观察结果提示了CD4介导的对CD4 + T/DC粘附的调节。此外，当用于预处理DC而非同种激活的CD4 + T细胞时，针对HLA II类分子的特异性抗体可抑制粘附。
