Hausmann M J, Rogachev B, Weiler M, Chaimovitz C, Douvdevani A
Department of Nephrology, Soroka Medical Center, Ben-Gurion University of the Negev, Faculty of Health Sciences, Beer-Sheva, Israel.
Kidney Int. 2000 Feb;57(2):476-86. doi: 10.1046/j.1523-1755.2000.00867.x.
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.
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.
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).
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.
为评估人腹膜间皮细胞（HPMCs）在腹膜炎期间免疫反应产生中的作用，我们测试了它们通过抗原呈递（AP）和分泌白细胞介素-15（IL-15）来激活T细胞的能力。IL-15是一种有效的白细胞激活剂，可刺激CD4 +、CD8 +、B细胞和自然杀伤（NK）细胞的增殖。
HPMCs和单核细胞来自六名接受择期腹部手术的志愿者患者。流式细胞术用于分析HPMCs上的人类淋巴细胞抗原-DR（HLA-DR）、细胞间粘附分子-1（ICAM-1）和B7分子。亲和纯化的CD4细胞用于AP检测。我们使用特异性酶联免疫吸附测定法检测干扰素-γ（IFN-γ）、IL-2和IL-15蛋白，并使用逆转录-聚合酶链反应进行mRNA分析。
IFN-γ处理后，HPMCs表达HLA-DR分子。ICAM-1分子高水平表达，未检测到B7-1和B7-2分子。使用抗CD3抗体（OKT3）通过T细胞刺激来检测HPMCs的辅助功能。HPMCs对于OKT3诱导的显著T细胞增殖至关重要。抗ICAM-1抗体阻断OKT3诱导的增殖。当使用破伤风类毒素（TT）或金黄色葡萄球菌α毒素作为抗原时，HPMCs作为有效的抗原呈递细胞。AP反应期间积累了IFN-γ、IL-2和IL-15。我们发现IL-15由HPMCs产生，并且IFN-γ以剂量依赖性方式上调其mRNA水平和蛋白分泌。我们还在接受持续腹膜透析治疗的患者的腹膜渗出液中检测到IL-15。与未感染患者（16.2±4.0 pg/mL，N = 7）相比，腹膜炎患者的IL-15水平升高（35.0±6.0 pg/mL，N = 10）。
HPMCs通过AP参与针对入侵病原体的腹膜免疫反应。对于此过程，ICAM-1是主要的辅助分子。此外，HPMCs可能通过分泌IL-15促进T细胞激活。
