Effects of several antibiotics on proliferation and regulatory T cell frequency in human lymphocytes stimulated with superantigen

我们以前的研究表明，超抗原刺激的人外周血单个核细胞(PBMC)具有持续产生IL-2的能力，可能是通过提高丝裂原活化蛋白激酶(MAPK)的活性来实现的。然而，这些异常激活与细菌超抗原或T细胞有丝分裂原刺激的外周血单核细胞中调节性T(Treg)细胞频率之间的关系尚不清楚。这些信息将有助于为克服自身免疫性疾病患者经常观察到的免疫抑制治疗的临床耐药性提供新的策略。然后，我们检测了超抗原刺激的PBMC中Treg的频率，以及几种抗生素、As_2O_3、抗癌药物和亲脂性维生素的作用。结果表明，As_2O_3和抗癌药物可增加活化的PBMC中Treg细胞的比例，而罗红霉素通过抑制JNK活性而抑制PBMC的增殖，而对Treg细胞无影响。在所检测的亲脂性维生素中，维生素K3和K5通过增加激活的PBMC中Treg的频率来抑制PBMC的增殖。我们还发现SLE患者PBMC中Treg频率与免疫抑制药物敏感性之间存在相关性。因此，细菌超抗原或T细胞有丝分裂原刺激的PBMC具有降低Treg频率的作用，而As_2O_3、维生素K_3和K5则通过提高激活的PBMC的Treg频率来抑制PBMC的增殖。

It has been suggested by our previous studies that superantigen-stimulated human peripheral-blood mononuclear cells (PBMCs) show continuous IL-2 producing ability, possibly via elevation of mitogen-activated protein kinase (MAPK) activity. However, it has still been unclear about relationship between these abnormal activations and the regulatory T (Treg) cell frequencies in PBMCs stimulted by bacterial superantigen or T cell mitogen. Such information would be useful for providing new strategies for overcoming clinical resistance to immunosuppressive therapy often observed in patients with autoimmune diseases. Then, we examined frequency of Treg in the superantigen-stimulated PBMCs, and the effects of several antibiotics, As_2O_3, anticancer agents, and lipophilic vitamins. We showed that As_2O_3and anticancer agents increase the frequency of Treg cells in the activated PBMCs, whereas roxithromycin inhibits PBMC proliferation without influence on Treg cells, via inhibition of JNK activity. Among the lipophilic vitamins examined, vitamin K3 and K5inhibited the PBMC proliferation via increase in Treg frequency in the activated PBMCs. We alsofound that there would be correlations between Treg frequencies and the sensitivities to immunosuppressive drugs in PBMCs of SLE patients. Thus, we concluded that PBMCs stimulated with bacterial superantigen or T cell mitogen have decreased Treg frequencies,and As_2O_3, vitamin K_3 and K5inhibit PBMC proliferation via promotion of Treg frequency in the activated PBMCs