B-LYMPHOCYTES THYMOCYTES AND PLATELETS ACCUMULATE HIGH dATP LEVELS IN SIMULATED ADA DEFICIENCY: 69

Abstract

Novel findings in vitro and in vivo obtained previously in simulated and inherited ADA deficiency were investigated using [8-14C] deoxyadenosine (dAR) in short-term experiments in intact human cells of the myeloid and lymphoid series.The studies produced several interesting results. (1) Tonsil-derived B-lymphocytes,thymocytes and platelets all accumulated detectable amounts of dATP even without ADA inhibition, and together with erythrocytes,extremely high dATP levels when ADA was inhibited by deoxycoformycin (dCF): varying amounts of dCF (20-60μm) were needed to completely inhibit ADA depending on the cell type. (2) By contrast,dATP accumulation by peripheral blood lymphocytes,granulocytes and macrophages was negligible without, and extremely low even with dCF. (3) B-lymphocytes showed a capacity equal to that of thymocytes in their ability to sustain the elevated dATP levels accumulated in ADA deficiency conditionsThe results support earlier findings which question the hypothesis that B-cells,compared with T-cells, have an inherent resistance to the toxic effects of dAR because of a lower ability to accumulate and sustain elevated dATP levels. They underline the difficulty in extrapolating from lysed or cultured cells to the situation in vivo in the peripheral blood. They suggest that the severe combined immunodeficiency in this disorder may be due to an equal sensitivity of B-lymphocytes and T-lymphocyte precursors to the toxic effects of dATP accumulation.