Accessory role of human peritoneal mesothelial cells in antigen presentation and T-cell growth

Kidney Int. 2000 Feb;57(2):476-86. doi: 10.1046/j.1523-1755.2000.00867.x.


Background: To assess the role of human peritoneal mesothelial cells (HPMCs) in the generation of an immune response during peritonitis, we tested their ability to activate T-cells by antigen presentation (AP) and by the secretion of interleukin-15 (IL-15). IL-15 is a potent leukocyte activator that stimulates the proliferation of CD4+, CD8+, and B and natural killer (NK) cells.

Methods: HPMCs and mononuclear cells were derived from six volunteer patients who underwent elective abdominal surgery. Flow cytometry was used to analyze human lymphocyte antigen-DR (HLA-DR), intercellular adhesion molecule-1 (ICAM-1), and B7 molecules on HPMCs. Affinity-purified CD4 cells were used for AP assays. We used a specific enzyme-linked immunosorbent assay to detect interferon-gamma (IFN-gamma), IL-2, and IL-15 protein and reverse transcription-polymerase chain reaction for mRNA analysis.

Results: HPMCs expressed HLA-DR molecules following IFN-gamma treatment. ICAM-1 molecules were expressed at high levels, and B7-1 and B7-2 molecules could not be detected. The accessory function of HPMCs was assayed by T-cell stimulation using anti-CD3 antibodies (OKT3). HPMCs were essential for a significant OKT3-induced T-cell proliferation. Anti-ICAM-1 antibodies blocked OKT3-induced proliferation. HPMCs served as effective antigen-presenting cells when Tetanus toxoid (TT) or Staphylococcus aureus-alpha-toxin were used as antigens. IFN-gamma, IL-2, and IL-15 accumulated during AP reactions. We found that IL-15 is produced by HPMCs, and IFN-gamma up-regulated its mRNA levels and protein secretion in a dose-dependent manner. We also detected IL-15 in the peritoneal effluent of patients undergoing continuous peritoneal dialysis treatment. In patients suffering from peritonitis, IL-15 levels were elevated (35.0 +/- 6.0 pg/mL, N = 10) as compared with noninfected patients (16.2 +/- 4.0 pg/mL, N = 7).

Conclusions: HPMCs participate in the peritoneal immune response against invading pathogens by AP. For this process, ICAM-1 is the major accessory molecule. In addition, HPMCs may contribute to T-cell activation by secretion of IL-15.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Antigen Presentation / immunology*
  • Bacterial Toxins / immunology
  • CD4-Positive T-Lymphocytes / cytology*
  • CD4-Positive T-Lymphocytes / immunology
  • Cell Division / immunology
  • Cells, Cultured
  • Epithelial Cells / cytology
  • Epithelial Cells / drug effects
  • Epithelial Cells / immunology*
  • Female
  • Flow Cytometry
  • Gene Expression / immunology
  • HLA-B7 Antigen / analysis
  • HLA-DR Antigens / analysis
  • Hemolysin Proteins / immunology
  • Humans
  • Immunosuppressive Agents / pharmacology
  • Intercellular Adhesion Molecule-1 / analysis
  • Interferon-gamma / pharmacology
  • Interleukin-15 / genetics
  • Interleukin-15 / immunology
  • Interleukin-15 / metabolism
  • Kidney Failure, Chronic / immunology
  • Kidney Failure, Chronic / therapy
  • Male
  • Middle Aged
  • Muromonab-CD3 / pharmacology
  • Oligonucleotide Probes
  • Peritoneal Dialysis, Continuous Ambulatory
  • Peritoneum / cytology*
  • Peritoneum / immunology
  • Peritonitis / immunology
  • Peritonitis / metabolism
  • RNA, Messenger / analysis
  • Tetanus Toxoid / immunology


  • Bacterial Toxins
  • HLA-B7 Antigen
  • HLA-DR Antigens
  • Hemolysin Proteins
  • Immunosuppressive Agents
  • Interleukin-15
  • Muromonab-CD3
  • Oligonucleotide Probes
  • RNA, Messenger
  • Tetanus Toxoid
  • staphylococcal alpha-toxin
  • Intercellular Adhesion Molecule-1
  • Interferon-gamma