McMillen M A, Kharma B, Fuortes M, Schaefer H C, McGowan E A, Baumgarten W K, Hoover E M
Department of Surgery, Bridgeport Hospital, Connecticut 06610.
J Surg Res. 1991 Jul;51(1):66-71. doi: 10.1016/0022-4804(91)90071-s.
Human peripheral blood mononuclear cells (H-PBMC) from 10 healthy donors were stimulated to proliferate with phytohemagglutinin lectin (PHA), anti-CD3 monoclonal antibody (mAb), and anti-CD3 mAb plus phorbol 12, myristate 13 acetate (TPA), a protein kinase C (PKC) agonist. Anti-CD3 mAb-mediated mitogenesis was 35-75% of that observed with PHA. When TPA was added to a dose of mAb that by itself did not cause mitogenesis, proliferation equal to 50-90% of the maximally mitogenic dose occurred. TPA did not enhance proliferation with maximally mitogenic doses of antibody. Dimethyl-prostaglandin E2, dibutyryl cyclic AMP, and forskolin (an adenyl cyclase agonist) inhibited PHA, anti-CD3, and anti-CD3/PMA-mediated mitogenesis. Cyclosporine (CSA) inhibited anti-CD3 and anti-CD3/TPA mitogenesis in a dose-dependent fashion. While CSA inhibited anti-CD3 and anti-CD3/TPA mitogenic signals, it did not affect PGE2 production by anti-CD3 mAb-stimulated H-PBMC. In the presence of CSA, PGE2 production in PHA-stimulated H-PBMC was increased. PGE2 inhibits lymphocyte proliferation via a cyclic AMP-mediated mechanism and may enhance maturation of suppressor cells. CSA inhibits anti-CD3 mAb and anti-CD3/TPA proliferative signals in H-PBMC yet has no effect or may even enhance production of suppressive PGE2. The maturation of antigen-specific suppressor cells elicited by CSA may involve active down-regulation of CD3 receptor and PKC-dependent events while PGE2 production continues.
来自10名健康供体的人外周血单个核细胞（H-PBMC）用植物血凝素（PHA）、抗CD3单克隆抗体（mAb）以及抗CD3 mAb加佛波醇12-肉豆蔻酸酯13-乙酸酯（TPA，一种蛋白激酶C（PKC）激动剂）刺激以使其增殖。抗CD3 mAb介导的有丝分裂原活性是PHA所观察到的活性的35%-75%。当将TPA添加到本身不会引起有丝分裂的一定剂量的mAb中时，会发生相当于最大促有丝分裂剂量50%-90%的增殖。TPA不会增强最大促有丝分裂剂量抗体介导的增殖。二甲基前列腺素E2、二丁酰环磷腺苷以及福斯可林（一种腺苷酸环化酶激动剂）抑制PHA、抗CD3以及抗CD3/PMA介导的有丝分裂原活性。环孢素（CSA）以剂量依赖的方式抑制抗CD3和抗CD3/TPA介导的有丝分裂原活性。虽然CSA抑制抗CD3和抗CD3/TPA介导的有丝分裂原信号，但它不影响抗CD3 mAb刺激的H-PBMC产生PGE2。在CSA存在的情况下，PHA刺激的H-PBMC中PGE2的产生增加。PGE2通过环磷腺苷介导的机制抑制淋巴细胞增殖，并且可能增强抑制性细胞的成熟。CSA抑制H-PBMC中抗CD3 mAb和抗CD3/TPA的增殖信号，但没有作用，甚至可能增强抑制性PGE2的产生。CSA引发的抗原特异性抑制性细胞的成熟可能涉及CD3受体和PKC依赖性事件的主动下调，而PGE2的产生仍在继续。
