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

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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