c-Rel expressed both by T cells and by APCs is required for the development of Th1 responses. Purified splenic APCs and naive CD4+ T cells were cultured at a ratio of 1:5 with 106 cells/ml in the presence of plate-bound anti-CD3 mAb (2 μg/ml). Each culture contained one type of APC (c-Rel+/+ or c-Rel–/–) and one type of T cell (c-Rel+/+ or c-Rel–/–). Five days later, cells were washed and restimulated with plate-bound anti-CD3 mAb (2 μg/ml) and anti-CD28 mAb (2 μg/ml) for 48 hours. Supernatants were collected and cytokine concentrations were determined by ELISA. Results are representative of two experiments.