PKA hyperactivation is responsible for dAdo-mediated suppression of T-cell function in ADA-deficient cells. CD4⁺ T cells were stimulated with 1 μg/mL coated anti-CD3 mAb in the presence or absence of dAdo (500 μM) with or without the inhibitor of cAMP-dependent protein kinase A, Rp-8-Br-cAMPS (150 μM). (A) Rate of proliferation was evaluated by [³H]thymidine incorporation after 48 hours. (B) Culture supernatants were collected for cytokine production quantification by ELISA after 18 (IL-2) or 48 (all other cytokine) hours. Percentages of inhibition with respect to the untreated condition are indicated. The data represent the mean plus or minus SD of 5 patients (ADA^−/− and GT) and 5 NDs from 1 of 3 independent experiments.