The immunosuppressive effect of chronic renal failure is correlated with an impaired proliferation of peripheral blood leukocytes in vitro. This is mainly due to an impaired function of the accessory cells rather than the T cells. Here we tried to define a missing accessory signal for T cell activation in hemodialysis patients. We substituted cell surface bound molecules by adding tumor cell lines to the in vitro assays that express different patterns of accessory molecules. Cell lines that express the costimulatory B7 molecule reconstituted the activation of patients' cells whereas B7 negative cells did not. The reconstitution was also achieved using mouse fibroblasts transfected with human B7 or by monoclonal antibodies that stimulate the B7 ligand CD28 on T cells. These data further emphasize that impaired leukocyte function in renal failure is due to an accessory cell defect, and that T cells of these patients have normal functional capacities when they get the costimulatory signals required. We demonstrate that it is the B7/CD28 pathway that reconstitutes cellular functions in the patients.(ABSTRACT TRUNCATED AT 250 WORDS)