The nuclear translocation of Rel proteins is impaired in patient T cells. T cells isolated from normal donors and RCC patients were stimulated for the times indicated with PMA (20 ng/mL) plus ionomycin (0.75 μg/mL). Thereafter, cytoplasmic and nuclear extracts derived from T cells of a healthy donor and from 2 RCC patients (KG and BH) were subjected to immunoblotting using antibodies to c-Rel, RelA, and p50 (NFκB1). In normals, there was a time-dependent increase in the nuclear level of Rel proteins that coincided with κB binding activity (data not shown). In patient T cells, there was no nuclear localization of Rel proteins after stimulation, even though they were constitutively expressed in the cytoplasm. There was also no induction of κB-specific DNA binding activity as defined by EMSA in nuclear extract from patient T cells (data not shown). These findings were consistent for all 7 patients and 10 normals.