Dual Effects of OK-432 on Mitogenic Response of Splenocytes to Concanavalin A

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Abstract
OK-432, a penicillin G-treatd, attenuated Streptoccus pyogenes preparation used to potentiate antitumor immunity of tumor bearing host, was studied for its effect of the concanavalin A (Con A)-induced mitogenesis of the host spleen cells. When mice were given a single i.p. injection of OK-432, there was a substantial increase in the mitogenic response of splenocytes, whereas multiple injections conversely resulted in a marked reduction of the mitogenic response, when the spleen cells were cultured at high cell densities > 5 x 105 cells/well. The reduced Con A-responsiveness in the latter was not restored by mixing spleen cells from mice given multiple OK-432 injections with those from normal mice. Splenic macrophages from OK-432-injected mice exhibited marked inhibitory activity against Con A-mitogenesis of normal splenocytes, while normal splenic macrophages failed to show such an effect. Splenic T cells from OK-432-injected mice also showed an inhibitory activity against Con A-mitogenesis of normal splenocytes and similar activity was also noted in normal splenic T cells. Therefore, the OK-432-spleen cells contain 2 types of suppressor cells; one is a newly elicited suppressor macrophage and the other is a suppresor T cell supposedly resident also in normal spleen cells. In the OK-432-injected spleen cells, accessory cell function for T cell Con A-mitogenesis was markedly reduced. The interleukin 2-producing ability of the OK-432-splenocytes was augmented more than that of normal splenocytes, indicating that multiple OK-432 injections also cause an increase in the helper T cell activity of the host spleen cells.