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The intracellular generation of reactive oxygen species (ROS) by 6-formylpterin and its effects on the human T cell functions were examined in vitro. When T cells isolated from fresh blood were incubated with 6-formylpterin for 1 hr, the oxygen consumption and concomitant ROS generation were observed. The incubation of T cells with 50–500 μM 6-formylpterin for 24 hr brought about the elevation of intracellular ROS without inducing cell death. In contrast, the incubation of T cells with exogenously administered hydrogen peroxide (H2O2) or other pterin derivatives (6-hydroxymethylpterin, pterin-6-carboxylic acid, pterin, neopterin, biopterin and folic acid) for 24 hr did not cause the intracellular ROS elevation. In the T cells stimulated with mitogenic lectin phytohemagglutinin (PHA) in conjunction with phorbol myristate acetate (PMA), 6-formylpterin suppressed the NF-κB-dependent transcription, the production of cytokines (IFN-γ and IL-2) and the cell proliferation. These suppressive effects of 6-formylpterin were all reversed by N-acetyl-l-cystein (NAC). However, 6-formylpterin did not inhibit the NF-κB-DNA binding of the nuclear extracts obtained from the PHA/PMA-stimulated T cells. Since the NF-κB-DNA binding assay performed in vitro merely shows the presence or absence of NF-κB subunit in the nuclear extracts but not guarantees the actual binding of NF-κB with DNA in the nucleus, these findings suggest that intracellular ROS generated by 6-formylpterin does not affect the translocation of NF-κB to the nucleus but that it inhibits the NF-κB-dependent transcription in the nucleus, resulting in the suppression of cytokine production and cell proliferation in the activated T cells.