Activation of murine lymphocytes by 2-mercaptoethanol and related thiol compounds and its mechanism. I. Relationship between mitogenic activities and augmenting effects on antibody synthesis in vitro.

Seven thiol compounds, namely, 2-mercaptoethanol (2-ME), alpha -thioglycerol (alpha -TG), dithiothreitol (DTT), cysteamine, L-cysteine (Cys), glutathione (GSH), and sodium thioglycollate (TGL) were examined for their mitogenic activities, the effects on mitogen-induced 3H-thymidine uptake, and the effects on antibody synthesis in vitro in murine spleen lymphocytes. All these thiols showed mitogenic activities in RPMI-1640 medium containing 10% fetal calf serum (FCS) with the following order of effectiveness: 2-ME greater than or equal to alpha -TG greater than DTT greater than cysteamine greater than Cys greater than or equal to GSH greater than TGL. A close correlation was observed between the enhancement of the response to lipopolysaccharide (LPS) and the mitogenic activities of these thiol compounds in their magnitude and dose-response profiles. The primary antibody response in vitro to sheep red blood cells (SRBC) (thymus-dependent) or dinitrophenyl (DNP)-Ficoll (thymus-independent) was augmented in a similar fashion by these compounds. T-cells depletion did not influence the enhancement by 2-ME of the antibody response to DNP-Ficoll. There was a discrepancy between the dose-response profiles of mitogenic activities of these compounds and their augmenting effects on antibody responses. Particularly, 2-ME and DTT significantly enhanced the antibody response to DNP-Ficoll or SRBC even at the nonmitogenic doses. Ethyl mercaptan (HSCH2 CH3) showed similar activities to 2-ME, but methylthioethanol (CH3 SCH2 CH2 OH) and ethanol (CH3 CH2 OH) were inactive, thus indicating that the thiol group would play an essential role in the above activities of 2-ME.