Landewé R B, Dijkmans B A, Verdonk M J, Breedveld F C, Daha M R, Miltenburg A M
Department of Rheumatology, Leiden University Hospital, The Netherlands.
Scand J Immunol. 1996 Jul;44(1):45-53. doi: 10.1046/j.1365-3083.1996.d01-280.x.
To investigate the regulation of interleukin-2 (IL-2) responsiveness of T cells, a human CD4+ T-cell clone with constitutive expression of IL-2 receptors was stimulated with recombinant IL-2 (rIL-2) in the presence or absence of immobilized anti-CD3 monoclonal antibodies (alpha CD3imm MoAb). Incubation of T cells with alpha CD3imm MoAb decreased IL-2-induced proliferation which could not be ascribed to the modulation of IL-2 receptor expression nor to cell death. Phorbol-myristate-acetate (PMA), an activator of protein kinase C (PKC), also induced down-regulation of IL-2 responsiveness. The alpha CD3sol MoAb, inducing Ca(2+)-mobilization without activating PKC, did not inhibit IL-2 responsiveness whereas cyclosporine A (CsA), a drug that inhibits the Ca(2+)-dependent activation pathway, did not prevent the induction of IL-2 hyporesponsiveness induced by alpha CD3imm MoAb. It is concluded that modulation of IL-2 responsiveness of T cells via the T-cell receptor/CD3 complex (TCR/CD3) may be mediated by a PKC-activating signal.
为了研究T细胞白细胞介素-2（IL-2）反应性的调节，在存在或不存在固定化抗CD3单克隆抗体（αCD3imm MoAb）的情况下，用重组IL-2（rIL-2）刺激具有IL-2受体组成性表达的人CD4 + T细胞克隆。用αCD3imm MoAb孵育T细胞可降低IL-2诱导的增殖，这既不能归因于IL-2受体表达的调节，也不能归因于细胞死亡。佛波醇-肉豆蔻酸酯-乙酸酯（PMA），一种蛋白激酶C（PKC）的激活剂，也诱导IL-2反应性的下调。诱导Ca（2+）动员而不激活PKC的αCD3sol MoAb不抑制IL-2反应性，而抑制Ca（2+）依赖性激活途径的药物环孢菌素A（CsA）不能阻止αCD3imm MoAb诱导的IL-2低反应性的诱导。结论是，通过T细胞受体/ CD3复合物（TCR / CD3）对T细胞IL-2反应性的调节可能由PKC激活信号介导。
