Dysregulation of TGF-βRII expression and loss of regulatory and effector T-cell function in patients with HAM/TSP. (A) CD4⁺CD25⁺ and CD4⁺CD25⁻ T cells from 2 healthy donors and 2 patients with HAM/TSP were analyzed for TGF-βRII mRNA expression by real-time RT-PCR (TaqMan). (B) CD4⁺CD25⁻Foxp3⁻ T cells from HAM/TSP patients (n = 5) were cultured for 5 days in the presence of a combination of the following: plate-bound anti-CD3 monoclonal antibody, soluble anti-CD28 monoclonal antibody, rhTGF-β1, and rhIL-2. On day 5, cells were analyzed for conversion into CD4⁺CD25⁺Foxp3⁺ T cells by flow cytometry. A statistically significant inverse correlation between the percentage CD25⁺Foxp3⁺ T-cell induction and the HTLV-I tax proviral load in PBMCs was observed in patients with HAM/TSP. (C) CD4⁺CD25⁺ and CD4⁺CD25⁻ T cells from healthy donors or patients with HAM/TSP were cultured separately or in coculture in the presence of anti-CD3 monoclonal antibody and irradiated accessory cells for 5 days. Proliferation was analyzed by [³H]-thymidine incorporation during the final 16 hours. Shown are the results of 2 independent experiments pairing a different healthy donor and HAM/TSP patient in each experiment. Error bars represent SEM.