Similarities in the Suppression of the Immune Response by Interferon and by a Thiol-Oxidizing Agent 1

Abstract

Abstract

Interferon and oxidized glutathione (GSSG) induced suppression of the C57B1/6 mouse spleen cell in vitro plaque-forming cell response. Both suppressions were reversible by 2-mercaptoethanol (2-ME), even when 2-ME was added to cultures up to 48 hr after inhibitors. Other sulfhydryl (SH) reducing agents had a similar effect. p-Hydroxymercuribenzene sulfonic acid (PHMB) is strictly a cell surface SH-binding agent, whose suppressive effects were not reversed by delayed addition of 2-ME to cultures. This suggested that 2-ME restored critical free SH groups on the surface of interferon- and GSSG-treated cells, while PHMB-altered SH groups were not restored to the original state. The data are consistent with a model of interferon induction of immunosuppression by binding to SH surface groups of the cell or by functioning as a surface thiol-oxidizing agent. This results in induction of a ribosome-associated protein kinase that blocks initiation of protein synthesis in both interferon- and GSSG-treated cells or cell lysates.