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

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.