Knoop C, Ismaili J, Bulté F, Abramowicz D, Estenne M, Goldman M
Department of Chest Medicine, Hôpital Erasme, Université Libre de Bruxelles, Brussels, Belgium.
Transplantation. 2000 Apr 15;69(7):1332-6. doi: 10.1097/00007890-200004150-00020.
Peripheral blood mononuclear cells (PBMC) of stable renal or cardiac transplant recipients were previously shown to respond to allogeneic cells but not to soluble protein antigens. The aim of the present study was to assess the T-cell and antigen-presenting cell (APC) functions of stable lung transplant (LT) recipients.
We obtained PBMC from 38 stable LT recipients. PBMC from healthy volunteers served as controls. PBMC were stimulated with either anti-CD3 monoclonal antibody, allogeneic PBMC, or tetanus toxoid (TT). T-cell activation was assessed by determination of interleukin (IL)-2 levels in culture supernatants; in some experiments, interferon-y levels were also determined. Patients' APC function was tested in a mixed leukocyte reaction using patients' PBMC as stimulators. The expression of class II MHC, B7.2, and CD40 molecules on patients' APC was determined by flow cytometry, and their production of IL-10 and IL-12 at the basal state and upon CD40 ligation was also measured.
Patients' T cells produced normal amounts of IL-2 in response to anti-CD3 monoclonal antibody and allogeneic PBMC. In contrast, the response of memory T cells to TT was severely blunted both in terms of IL-2 and interferon-y production. Patients' PBMC were poor stimulators in mixed leukocyte reaction, and class II MHC expression on patients' monocytes was significantly reduced. Patients' APC presented a modest but significant increase in basal IL-10 production and produced significantly less IL-12 upon CD40 ligation than control APC.
T cells from stable LT recipients respond normally to stimuli that do not depend on autologous APC. The major impairment in the T-cell response to TT is caused by APC dysfunction, which involves decreased class II MHC expression and deficient IL-12 synthesis.
先前研究表明，稳定期肾移植或心脏移植受者的外周血单个核细胞（PBMC）对同种异体细胞有反应，但对可溶性蛋白抗原则无反应。本研究旨在评估稳定期肺移植（LT）受者的T细胞和抗原呈递细胞（APC）功能。
我们从38名稳定期LT受者中获取PBMC。来自健康志愿者的PBMC作为对照。PBMC用抗CD3单克隆抗体、同种异体PBMC或破伤风类毒素（TT）刺激。通过测定培养上清液中的白细胞介素（IL）-2水平评估T细胞活化；在一些实验中还测定了干扰素-γ水平。使用患者的PBMC作为刺激物，通过混合淋巴细胞反应测试患者的APC功能。通过流式细胞术测定患者APC上II类MHC、B7.2和CD40分子的表达，并测量其在基础状态和CD40连接后的IL-10和IL-12产生情况。
患者的T细胞在抗CD3单克隆抗体和同种异体PBMC刺激下产生正常量的IL-2。相比之下，记忆T细胞对TT的反应在IL-2和干扰素-γ产生方面均严重减弱。患者的PBMC在混合淋巴细胞反应中是较差的刺激物，患者单核细胞上II类MHC的表达显著降低。患者的APC基础IL-10产生有适度但显著的增加，并且在CD40连接后产生的IL-12明显少于对照APC。
稳定期LT受者的T细胞对不依赖自体APC的刺激反应正常。T细胞对TT反应的主要损害是由APC功能障碍引起的，这涉及II类MHC表达降低和IL-12合成不足。
