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.

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.