The metabolism of deoxyguanosine and guanosine in human B and T lymphoblasts. A role for deoxyguanosine kinase activity in the selective T-cell defect associated with purine nucleoside phosphorylase deficiency

摘要

pPurine nucleoside phosphorylase (NP; EC 2.4.2.1) deficiency is associated with defective T-cell and normal B-cell immunity. Biochemical mechanisms were investigated by measuring deoxyguanosine and guanosine metabolism in normal T and B lymphoblasts and NP-deficient B lymphoblasts. Deoxyguanosine kinase activity was specifically measured by using an anti-NP antibody to prevent alternative-product formation. Kinase activity towards deoxyguanosine was significantly higher in T-cells, whereas NP activity was similar in both B- and T-cells. Only in T-cells was dGTP produced from exogenous deoxyguanosine, and this was prevented by the simultaneous addition of deoxycytidine, which resulted in a concomitant increase in GTP synthesis. Inhibition by 8-aminoguanosine of NP activity in T lymphoblasts increased formation of dGTP and decreased that of GTP from deoxyguanosine and decreased the formation of GTP from guanosine. These data suggest a central role for deoxyguanosine kinase activity in the T-cell selectivity of the immune defect./p