Monocyte-mediated suppression of mitogen responses of lymphocytes in uremic patients.

In the present experiment, we investigated the mechanism of the suppressed mitogen responses of peripheral blood mononuclear cells (PBMC) from uremic patients. We used phytohemagglutinin (PHA) and concanavalin A (Con A) as T cell mitogens, pokeweed mitogen (PWM) as a T cell-dependent B cell mitogen, and Staphylococcus aureus Cowan I (STA) as a T cell-independent B cell mitogen. PBMC from uremic patients showed significantly suppressed responses to PHA (p less than 0.05), Con A (p less than 0.05) and STA (p less tha 0.01) compared with those from healthy controls, but there was no significant difference in PWM response. However, these suppressed responses to PHA and Con A were markedly restored by depletion of phagocytic cells from PBMC. Although STA responses were also restored markedly in uremic patients, some patients still showed lower responsiveness to STA indicating the possibility of functional B cell defects. To further clarify the mechanism of the suppressed responses to mitogens, PBMC or nonphagocytic cells from uremic patients were cocultured with control T cells in the presence of PHA, or the effects of adherent cells from uremic patients on PHA responses of autologous or allogeneic control T cells were studied. From these experiments, it was suggested that the suppressed responses of PBMC to mitogens in uremia were mediated by monocytes.