Galandrini R, Galluzzo E, Albi N, Grossi C E, Velardi A
Department of Clinical Medicine, Pathology, and Pharmacology, University of Perugia, Italy.
J Immunol. 1994 Jul 1;153(1):21-31.
Lymphohematopoiesis, cell matrix adhesion, homing of leukocytes, T cell activation, and tumor metastasis are mediated through the CD44 family of cell surface receptors. We have recently shown that anti-CD44 mAb trigger protein tyrosine kinase-dependent activation of T cell effector functions. Here, we show that hyaluronate (HA), a CD44 ligand, in conjunction with CD3/TCR-mediated stimuli, is costimulatory for human peripheral blood T cell proliferation, for IL-2 production by Th clones, and for release of trypsin-like esterase by cytolytic T cell clones. A human T cell line, HUT-78, was found to bind HA and on HA coating it was used as a target for cytolytic T cell clones. After anti-CD3 stimulation, CD3+/CD8+ clones acquire the ability of lysing HA-coated HUT-78 cells more efficiently than the same HA-uncoated targets. Resting peripheral blood T cells and T cell clones do not adhere to HA-coated plates. However, 24-h anti-CD3 mAb stimulation gives them the transient ability to bind HA. HA adhesion of activated T cells and T cell clones, as well as that of T cell lines, is blocked by one anti-CD44 mAb (J-173). Two other anti-CD44 mAbs induce a 10-fold increase in HA adhesiveness of anti-CD3-stimulated peripheral blood T cells. This impressive HA adhesiveness is also readily blocked by J-173 anti-CD44 mAb. These data indicate that 1) HA is costimulatory for human T cell effector functions in conjunction with CD3/TCR-mediated stimuli, 2) the capacity to bind HA is acquired by resting T cells and T cell clones after anti-CD3 stimulation, and 3) HA binding occurs via specific interaction with CD44 molecules expressed on activated T cells.
淋巴细胞生成、细胞与基质的黏附、白细胞归巢、T细胞活化以及肿瘤转移均通过细胞表面受体CD44家族介导。我们最近发现，抗CD44单克隆抗体可触发蛋白酪氨酸激酶依赖性的T细胞效应功能激活。在此，我们表明，透明质酸（HA）作为CD44的配体，与CD3/TCR介导的刺激协同作用，对人外周血T细胞增殖、Th克隆产生白细胞介素-2以及细胞毒性T细胞克隆释放胰蛋白酶样酯酶具有共刺激作用。发现人T细胞系HUT-78能结合HA，并且在HA包被后用作细胞毒性T细胞克隆的靶标。抗CD3刺激后，CD3+/CD8+克隆比相同的未包被HA的靶标更有效地获得裂解HA包被的HUT-78细胞的能力。静息外周血T细胞和T细胞克隆不黏附于HA包被的平板。然而，24小时抗CD3单克隆抗体刺激赋予它们短暂结合HA的能力。活化的T细胞、T细胞克隆以及T细胞系与HA的黏附被一种抗CD44单克隆抗体（J-173）阻断。另外两种抗CD44单克隆抗体使抗CD3刺激的外周血T细胞与HA的黏附性增加10倍。这种显著的HA黏附性也很容易被J-173抗CD44单克隆抗体阻断。这些数据表明：1）HA与CD3/TCR介导的刺激协同作用，对人T细胞效应功能具有共刺激作用；2）静息T细胞和T细胞克隆在抗CD3刺激后获得结合HA的能力；3）HA结合通过与活化T细胞上表达的CD44分子特异性相互作用发生。
