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

Michael Joseph Hausmann, Boris Rogachev, Michal Weiler, Cidio Chaimovitz, Amos Douvdevani

Research output: Contribution to journalArticlepeer-review

54 Scopus citations

Abstract

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-γ (IFN-γ), IL-2, and IL-15 protein and reverse transcription-polymerase chain reaction for mRNA analysis. Results. HPMCs expressed HLA-DR molecules following IFN-γ 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-α-toxin were used as antigens. IFN-γ, IL-2, and IL-15 accumulated during AP reactions. We found that IL-15 is produced by HPMCs, and IFN-γ 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.

Original languageEnglish
Pages (from-to)476-486
Number of pages11
JournalKidney International
Volume57
Issue number2
DOIs
StatePublished - 1 Jan 2000

Keywords

  • Immune response
  • Interferon-γ
  • Interleukin-15
  • Leukocytes
  • Peritonitis
  • T lymphocytes

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