Cesano A, Visonneau S, Deaglio S, Malavasi F, Santoli D
The Wistar Institute of Anatomy and Biology, Philadelphia, PA 19104, USA.
J Immunol. 1998 Feb 1;160(3):1106-15.
Human CD38 is a type II transmembrane glycoprotein that regulates lymphocyte adhesion, proliferation, and cytokine production. The mAb Moon-1 recognizes a ligand for CD38 (CD38L) and specifically inhibits CD38-mediated cell adhesion. To analyze the role of CD38 and its ligand in MHC-nonrestricted T cell activation, we examined the effects of Moon-1 and the anti-CD38 mAb IB4 on the effector functions of the IL-2-dependent T cell line TALL-104 (CD3/TCR-alphabeta+, CD8+, CD56+) and of LAK cells (90% CD3+). TALL-104 cells were almost 100% reactive with both mAbs, whereas the reactivity of LAK cells for IB4 and Moon-1 ranged from 10 to 60% among different donors. From 78 to 94% of the cytotoxic CD8+/CD56+ LAK subset was CD38L+. Like mAb OKT3 (anti-CD3), and at variance with IB4, Moon-1 drastically enhanced the cytotoxicity of TALL-104 and CD8+ LAK cells against a resistant tumor target. Granule exocytosis did not appear to play a role in Moon-1-induced cytotoxicity. Moreover, neither IB4 nor Moon-1 induced [Ca2+]i mobilization in LAK and TALL-104 cells. Whereas stimulation of CD3 and CD38 resulted in a dramatic induction of cytokine (granulocyte-macrophage-CSF, IFN-gamma, TNF-alpha, and TNF-beta) release by both TALL-104 and LAK cells, ligation of CD38L was not followed by cytokine production in TALL-104 cells. Thus, cytotoxicity and cytokine release are independently regulated, at least in this system. These data demonstrate that CD38 and its ligand can regulate some T cell functions using signaling pathways distinct from those of CD3.
人CD38是一种II型跨膜糖蛋白，可调节淋巴细胞黏附、增殖和细胞因子产生。单克隆抗体Moon-1识别CD38的一种配体（CD38L），并特异性抑制CD38介导的细胞黏附。为了分析CD38及其配体在MHC非限制性T细胞活化中的作用，我们检测了Moon-1和抗CD38单克隆抗体IB4对IL-2依赖性T细胞系TALL-104（CD3/TCR-αβ+、CD8+、CD56+）和LAK细胞（90% CD3+）效应功能的影响。TALL-104细胞与这两种单克隆抗体的反应性几乎为100%，而不同供体的LAK细胞对IB4和Moon-1的反应性在10%至60%之间。78%至94%的细胞毒性CD8+/CD56+ LAK亚群为CD38L+。与单克隆抗体OKT3（抗CD3）一样，与IB4不同，Moon-1显著增强了TALL-104和CD8+ LAK细胞对耐药肿瘤靶标的细胞毒性。颗粒胞吐似乎在Moon-1诱导的细胞毒性中不起作用。此外，IB4和Moon-1均未在LAK和TALL-104细胞中诱导[Ca2+]i动员。虽然CD3和CD38的刺激导致TALL-104和LAK细胞大量诱导细胞因子（粒细胞-巨噬细胞集落刺激因子、干扰素-γ、肿瘤坏死因子-α和肿瘤坏死因子-β）释放，但TALL-104细胞中CD38L的连接并未伴随细胞因子产生。因此，至少在这个系统中，细胞毒性和细胞因子释放是独立调节的。这些数据表明，CD38及其配体可以使用与CD3不同的信号通路调节某些T细胞功能。
