Monocyte-Mediated Suppression of Mitogen Responses of Lymphocytes in Uremic Patients

Abstract

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 < 0.05), Con A (p < 0.05) and STA (p < 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.

Suppressor Resident Peritoneal Macrophages and Peritonitis Incidence in Continuous Ambulatory Peritoneal Dialysis

“…Peritoneal macrophages and supernatant fac tors of uremic patients undergoing CAPD appeared cap able of exercising the same activities, but the degree of macrophage inhibitory effect on lymphocyte activation dif fered within the population of CAPD patients [20], Similarly to that observed by other authors, our CAPD patient population can be subdivided into that in which peritonitis incidence was extremely high and that in which the peritonitis developed rather rarely [21], The first patient group showed high suppressor activity on control nonadherent cell response to mitogens. On the contrary, peritoneal macrophages from normal subjects or from CAPD patients with few bacterial peritonitis episodes demonstrated very low suppressor activity.…”

Depressed Natural Killer Cell Activity in Uremia

“…Decreased delayed hypersensitivity (1], decreased OKT4/OKT8 ratio [2] and reduced lymphocyte response to mitogens [1,[3][4][5] have been reported in patients on maintenance HD. A high incidence of neoplasms [6,7] and tuberculosis [8,9] has also been found in uremic patients.…”

“…Prostaglandin E2 produced by monocytes has been reported to regulate IL-2 augmentation of NK cell activ ity [25]. Moreover, in uremic patients, the depletion of adherent monocytes from PBMC [3][4][5] and the addition of indomethacin, a cyclooxygenase inhibitor [4], have been reported to restore impaired lymphocyte responses to mitogens. Although the precise mechanism of a poor response of NK cells to 1 L-2 in uremia also remains to be clarified, it is speculated that activated monocytes by uremic toxin(s) produce excessive prostaglandin E2, re sulting in the depressed response of NK cells to IL-2.…”

“…Decreased delayed hypersensitiv ity [1], decreased OKT4/OKT8 ratio [2] and reduced lymphocyte response to mitogens [I, [3][4][5] have been found in uremic patients. These findings indicate that cell-mediated immunity is impaired in uremia.…”

Defective Radioresistant Suppressor Cell Activity in Hemodialysis Patients

“…The mechanisms responsible for this rela tive anergy are unknown but uremic toxins and malnutri tion are the factors more commonly implicated [1][2][3]. Although several alterations of humoral immunity have been reported [1,2,4,5] the uremic immunodeficiency is mostly attributed to a deficiency of cell-mediated immu nity [1,[6][7][8]. Lymphopenia [2], reduced numbers of OKT 4 + cells [9], impaired cell-mediated immune reactions such as unresponsiveness to skin tests [2], prolonged skin graft survival [10], poor graft versus host reaction [4] and a low response to T-dependent mitogens [1,[6][7][8] are some of the alterations that have been described in these pa tients.…”