Inhibition of in Vitro Lymphocyte Proliferation and B Cell Differentiation by Deoxyguanosine: Evidence for Separate Mechanisms
A number of patients with a selective cellular immunodeficiency associated with a deficiency of purine nucleoside Phosphorylase (PNP) have been described (1,2). In PNP deficiency, one of the accumulated substrates of the enzyme i.e. deoxyguanosine (dGuo) appears to be extremely toxic to lymphoid cells in particular to thymocytes (3). The proposed pathophysiologic mechanism in PNP deficiency implies lymphocyte “specific” phosphorylation of dGuo into dGTP which inhibits the reduction of CDP by ribonucleotide reductase; as a result intracellular dCTP is depleted leading to a disturbance of lymphocytic DNA synthesis (4). In vitro studies e.g. on lymphoblastoid cell lines have shown that dGuo inhibits the in vitro growth of T cell lines whereas B cell lines are relatively unaffected(5,6). Most studies have not been performed under PNP-deficient conditions.
KeywordsPeripheral Blood Lymphocyte Lymphocyte Proliferation Lymphoblastoid Cell Line Ribonucleotide Reductase Normal Lymphocyte
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