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-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.
Hausmann
M J
MJ
Department of Nephrology, Soroka Medical Center, Ben-Gurion University of the Negev, Faculty of Health Sciences, Beer-Sheva, Israel.
Rogachev
B
B
Weiler
M
M
Chaimovitz
C
C
Douvdevani
A
A
D000328:Adult; D017951:Antigen Presentation / Q000276:immunology*; D001427:Bacterial Toxins / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology* / Q000276:immunology; D002455:Cell Division / Q000276:immunology; D002478:Cells, Cultured; D004847:Epithelial Cells / Q000166:cytology / Q000187:drug effects / Q000276:immunology*; D005260:Female; D005434:Flow Cytometry; D015870:Gene Expression / Q000276:immunology; D015793:HLA-B7 Antigen / Q000032:analysis; D006684:HLA-DR Antigens / Q000032:analysis; D006460:Hemolysin Proteins / Q000276:immunology; D006801:Humans; D007166:Immunosuppressive Agents / Q000494:pharmacology; D018799:Intercellular Adhesion Molecule-1 / Q000032:analysis; D007371:Interferon-gamma / Q000494:pharmacology; D019409:Interleukin-15 / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D007676:Kidney Failure, Chronic / Q000276:immunology / Q000628:therapy; D008297:Male; D008875:Middle Aged; D016853:Muromonab-CD3 / Q000494:pharmacology; D015345:Oligonucleotide Probes; D010531:Peritoneal Dialysis, Continuous Ambulatory; D010537:Peritoneum / Q000166:cytology* / Q000276:immunology; D010538:Peritonitis / Q000276:immunology / Q000378:metabolism; D012333:RNA, Messenger / Q000032:analysis; D013745:Tetanus Toxoid / Q000276:immunology
D001427:Bacterial Toxins; D015793:HLA-B7 Antigen; D006684:HLA-DR Antigens; D006460:Hemolysin Proteins; D007166:Immunosuppressive Agents; D019409:Interleukin-15; D016853:Muromonab-CD3; D015345:Oligonucleotide Probes; D012333:RNA, Messenger; D013745:Tetanus Toxoid; C021091:staphylococcal alpha-toxin; D018799:Intercellular Adhesion Molecule-1; D007371:Interferon-gamma