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Published on: October 17, 2017
Altered monocyte function in uremia
R A Gibbons1, O M Martinez, M R Garovoy
1Immunogenetics and Transplantation Laboratory, Department of Surgery, University of California, San Francisco 94143.
Abstract:
Uremia appears to suppress immune function predisposing patients to infections. When the defect in cellular immunity was studied by exposing mononuclear cells (MNC) from uremic patients and controls to tetanus toxoid, diptheria toxoid, or Candida albicans antigen in vitro, the uremic cells were far less responsive. Monocytes and T cells, which are both involved in the proliferative response to soluble antigens, were isolated from MNC of uremic patients and HLA class II matched controls and incubated with tetanus toxoid. Tetanus toxoid-pulsed uremic monocytes were unable to stimulate the proliferation of HLA identical control T lymphocytes. Lymphocytes from uremic patients, however, were stimulated by tetanus toxoid-pulsed control monocytes. Therefore, the ability of monocytes to function as accessory cells is severely affected by uremia. The uremic monocytes were FcR+, produced IL-1 beta, and expressed levels of HLA class II antigens comparable to controls. Although the biochemical defect in uremic monocytes remains unknown, the abnormality could explain many of the immunological changes of uremia.
Insights
Uremia impairs immune cells, particularly monocytes, hindering their ability to stimulate T cells. This defect in monocyte accessory cell function contributes to the increased infection risk in uremic patients.
Area of Science:
- Immunology
- Nephrology
- Cell Biology
Background:
- Uremia is associated with immune suppression and increased susceptibility to infections.
- Cellular immunity defects are observed in patients with uremia.
- Mononuclear cells (MNC) from uremic patients show reduced responsiveness to antigens in vitro.
Purpose of the Study:
- To investigate the defect in cellular immunity in uremic patients.
- To determine the role of monocytes and T cells in the impaired immune response of uremia.
- To elucidate the function of monocytes as accessory cells in uremic patients.
Main Methods:
- Exposing MNC from uremic patients and controls to various antigens (tetanus toxoid, diphtheria toxoid, Candida albicans antigen) in vitro.
- Isolating monocytes and T cells from MNC of uremic patients and HLA class II matched controls.
- Incubating tetanus toxoid-pulsed uremic monocytes with control T lymphocytes and vice versa.
- Analyzing the proliferative response of T lymphocytes.
Main Results:
- Uremic MNC exhibited significantly lower responsiveness to antigens compared to controls.
- Tetanus toxoid-pulsed uremic monocytes failed to stimulate proliferation in HLA-identical control T lymphocytes.
- T lymphocytes from uremic patients could be stimulated by tetanus toxoid-pulsed control monocytes.
- Uremic monocytes displayed normal FcR expression, IL-1 beta production, and HLA class II antigen levels.
Conclusions:
- Uremia severely impairs the accessory cell function of monocytes.
- The defect in monocyte accessory function is a key factor in the immunological abnormalities observed in uremia.
- The precise biochemical defect in uremic monocytes requires further investigation but likely explains immune dysfunction and infection risk.
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