Spinozzi F, Nicoletti I, Agea E, Belia S, Moraca R, Migliorati G, Riccardi C, Grignani F, Bertotto A
Department of Internal Medicine, University of Perugia, Italy.
Immunology. 1995 Nov;86(3):379-84.
Activation of immature thymocytes or transformed T lymphocytes via T-cell receptor (TCR)/CD3 signalling can induce programmed cell death (apoptosis). Recent data indicate that anti-CD3/TCR monoclonal antibodies (mAb) also trigger apoptosis in activated (but not resting) mature peripheral blood T lymphocytes. Here we report that triggering of resting CD4-CD8-TCR alpha beta+ and/or TCR gamma delta+ via the alternative CD2-dependent activation pathway is able to induce programmed cell death. A pair of mitogenic anti-CD2 mAb provoked a dramatic rise in [Ca2+]i that was almost entirely sustained by extracellular fluxes, and the inhibition of membrane [Ca2+/Mg2+] ATPase. The resulting endonuclease activation was able to induce DNA fragmentation, as revealed by propidium iodide staining and gel electrophoresis. Induction of apoptosis was prevented by the presence of interleukin-4 (IL-4) as well as by endonuclease inactivation with 100 microM ZnCl2, but enhanced by the contemporary block of protein kinase C. Thus it seems that in resting T lymphocytes the strong calcium signal delivered by the alternative CD2 activation pathway may act as a negative apoptotic signal in both alpha beta and gamma delta T cells with low (non-major histocompatibility complex restricted) antigenic affinity, so limiting the extension of polyclonal T-cell growth.
通过T细胞受体（TCR）/CD3信号传导激活未成熟胸腺细胞或转化的T淋巴细胞可诱导程序性细胞死亡（凋亡）。最近的数据表明，抗CD3/TCR单克隆抗体（mAb）也能触发活化的（而非静止的）成熟外周血T淋巴细胞凋亡。在此我们报告，通过替代性CD2依赖性激活途径触发静止的CD4-CD8-TCRαβ+和/或TCRγδ+能够诱导程序性细胞死亡。一对促有丝分裂的抗CD2 mAb引起细胞内钙离子浓度（[Ca2+]i）急剧升高，这几乎完全由细胞外钙离子内流以及膜[Ca2+/Mg2+]ATP酶的抑制所维持。如碘化丙啶染色和凝胶电泳所示，由此导致的核酸内切酶激活能够诱导DNA片段化。白细胞介素-4（IL-4）的存在以及用100微摩尔/升氯化锌使核酸内切酶失活可阻止凋亡的诱导，但蛋白激酶C的同时阻断会增强凋亡诱导。因此，在静止T淋巴细胞中，替代性CD2激活途径传递的强烈钙信号可能在具有低（非主要组织相容性复合体限制）抗原亲和力的αβ和γδ T细胞中充当负性凋亡信号，从而限制多克隆T细胞生长的扩展。
