Suppression of Human Lymphocyte Responses in Chronic Renal Failure Mediated by Adherent Cells: Analysis in Serum-free Media

Concanavalin A (Con A)-induced proliferative responses by mononuclear leukocytes (MNCs) from patients with chronic renal failure (CRF) who were undergoing maintenance hemodialysis were studied with serum-free media to analyze leukocyte function independent of either uremic or normal serum factors. When we increased the number of cultured MNCs by 2.5- to fivefold over that normally used in microcultures and reduced the mitogen concentration, Con A induced proliferative responses 10- to 1000-fold higher than those in unstimulated cultures. In 12 of 15 patients with CRF observed, Con A-induced MNC responses were significantly depressed as compared with those in age- and sex-matched controls. Responses in 10 of these 12 patients with CRF improved significantly immediately after dialysis, but the improvement was only temporary. With MNCs from patients with CRF before dialysis, removal of adherent cells significantly improved their responses to Con A. Similar increases with adherent cell depletion were not found either in cultures of control MNCs or in patient MNCs after dialysis. Indomethacin, a cyclooxygenase inhibitor, added to unseparated MNCs from patients before dialysis, significantly increased responses in 13 of 15 patients. This effect of indomethacin was found less frequently in MNC cultures from normal persons or from patients with CRF after dialysis. Nonadherent lymphocytes from patients with CRF were not abnormally sensitive to inhibition by exogenously added prostaglandin E2. We conclude that MNCs from most patients with CRF have depressed reactivity when cultured without serum and that responses improve temporarily after dialysis. Adherent cells are largely responsible for inhibiting lymphocyte responses, and monocyte-released cyclooxygenase products appear to mediate much of this suppression.