The modulation of IL-2 dependent proliferation of CTLL-2 cells by 2-methyl-thiazolidine-2,4-dicarboxylic acid

Abstract

It is known that cysteine and other thiol compounds are able to modulate the immune response. The extracellular concentration of cysteine was shown to determine the intracellular level of glutathione (GSH). Thus cysteine, by enhancing GSH production, is able to affect some T-cell functions like IL-2 dependent cell proliferation and the generation of cytotoxic T cells. However, physiologically blood plasma cysteine is maintained at a very low concentration. The use of cysteine as a therapeutic compound in vivo is strongly limited due to its cytotoxicity. Recent studies demonstrate that N-acetyl-cysteine (NAC) as well as a variety of thiazolidine derivatives (TDs), which are the products of the reaction of l-cysteine with carbonyl compounds, could serve as a ‘delivery’ system for cysteine into the cell. In the present study, we have shown that 2-methyl-thiazolidine-2,4,-dicarboxylic acid (CP), the product of condensation of l-cysteine and pyruvate, strongly increases the proliferation of one particular cell line, IL-2 dependent CTLL-2 cells. We have also shown that this compound significantly increases the intracelullar level of non-protein sulfhydryls (NPSH), but we did not find any correlation between NPSH levels and cell viability and proliferation. In contrast to CP, free cysteine showed its toxic properties by affecting cell viability of different cell lines and also by cancelling the influence of CP on the proliferation of CTLL cells.)