Abstract
We previously showed that deoxyguanosine (dGuo) is toxic not only to purine nucleoside phosphorylase (PNP) deficient T cells but also to normal peripheral blood T and B lymphocytes activated in vitro with appropriate mitogens or antigens. The dGuo-mediated toxicity of proliferating T and B lymphocytes is accompanied by intracellular accumulation of guanine ribonucleotides like GDP and GTP. DeoxyGuo does not affect the expression of interleukin-2 (Il-2) receptors on T cells activated with mitogens. The latter finding indicates that the process of T cell activation up to the appearance of Il-2 receptors is insensitive to dGuo despite ongoing accumulation of GTP. However, addition of Il-2 to T lymphocytes activated with mitogens in the presence of dGuo and expressing Il-2 receptors does not induce T cell proliferation. Binding studies using radiolabelled Il-2 showed that neither the number of high affinity receptors nor that of low affinity receptors is significantly affected by dGuo. We therefore hypothesize that the effect of dGuo and hence of GTP is at the level of signal transduction following the interaction of Il-2 with the Il-2 receptor.
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Scharenberg, J., Rijkers, G., Staal, G. et al. 185 THE MECHANISM OF DEOXYGUANOSINE MEDIATED TOXICITY IN PROLIFERATING HUMAN PERIPHERAL BLOOD T LYMPHOCYTES. Pediatr Res 24, 142 (1988). https://doi.org/10.1203/00006450-198807000-00209
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DOI: https://doi.org/10.1203/00006450-198807000-00209