Sodium diethyl dithiocarbamate (DE-DTC) is a lipophilic low molecular weight sulphur compound previously demonstrated to be a potent immunomodulator but cytotoxic in vitro. In this work, we studied the effects on a hydrophilic analog of DE-DTC, sodium N-Methyl-D-glucamine dithiocarbamate (NMG-DTC) on immune responses to a hapten carrier conjugate and on mitogen-induced lymphoproliferation. NMG-DTC, in contrast to DE-DTC, did not modify the responses to a hapten-carrier conjugate. The immunomodulatory activity of DE-DTC appeared to be linked with its lipophilicity. NMG-DTC had a slight inhibitory effect on thymidine incorporation by lymphocytes stimulated by mitogens as compared to that of DE-DTC. DE-DTC was cytotoxic possibly at the cell membrane level; cytotoxicity was not related to the chelating properties of DE-DTC in the culture medium. On the other hand, NMG-DTC appeared to be a less cytotoxic molecule. Therefore it could be useful to study the effects of the dithiocarbamate moiety at the cellular level.
The incorporation of 3H-thymidine in newly formed DNA was studied in guinea pig spleen cells stimulated by phytohemagglutinin (PHA) and/or concanavalin A (Con A). In spleen cells stimulated by PHA, two peaks of thymidine uptake were observed for two different doses of lectin whatever the number of cultured cells. Furthermore, thymidine uptake is proportional to the number of the cultured cells. During Con A-induced mitogenesis, two peaks were also observed but only when using a great concentration of cells. Maximal thymidine incorporation depended on both the cell number and the concentration of Con A. When cells were stimulated by both PHA and Con A, thymidine uptake was strongly depressed as compared to the one observed using PHA or Con A alone. On the other hand, supernatants from unstimulated spleen cells had opposite effects on blastogenesis induced by Con A or by PHA; they depressed PHA-induced blastogenesis while enhancing the one induced by Con A. These results suggest that, in guinea pigs, both PHA and Con A induce thymidine incorporation in at least two lymphocyte populations through different mechanisms. This heterogeneity of lectin-induced T cell mitogenesis has to be taken in account when studying the mechanisms by which the immunomodulators are active at the T cell level.
Normal guinea pig serum was fractionated by filtration through a Sephacryl S200 column. The various fractions were assayed on concanavalin A and phytohemagglutinin-induced mitogenesis as measured by 3H-thymidine uptake in newly formed DNA. α-Globulin, γ-globulins and albumin were shown to modulate lymphoproliferation. The enhancing or depressing effects of these various fractions depended upon the nature and dose of the mitogen used, the concentration of the fraction added, and the time interval between the addition of fractions and the addition of mitogens. The results suggest that serum fractions can at least modulate the immune response through their activity on the proliferation of lympohocytes.
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