Dlubek D, Turlej E, Sedzimirska M, Lange J, Lange A
Institute of Immunology and Experimental Therapy, Polish Academy of Science, Wroclaw, Poland.
Transplant Proc. 2010 Oct;42(8):3277-9. doi: 10.1016/j.transproceed.2010.07.026.
Interleukin-17A is a hallmark of a subset of CD4+ lymphocytes called T(H)17. Allogeneic hematopoietic stem cell transplantation (HSCT) induces an immune response that facilitates graft acceptance, but if clinically apparent as acute graft-versus-host disease (aGvHD), it may adversely affect transplantation outcomes. TH17 cells are involved in the inflammatory processes associated with several diseases, including inflammatory bowel disease (IBD) as a prototype. In this study we investigated the presence of IL-17-producing cells among peripheral blood mononuclear cells (PBMC) of patients after HSCT. The 48 patients of median age 45 years (range, 1.0-64 years), experienced hematologic malignancies (n=45) or nonmalignant disorders (n=3), treated with matched unrelated (n=24) or sibling (n=24) transplants. We examined IL-17-producing cells in alloreactive reactions after HSCT. PBMC were stimulated with BD Leukocyte Activation Cocktail (Ionomycin, Brefeldin A, and phorbol myristic acetate (PMA)) in the presence of BD GolgiStop. After stimulation the cells were labeled with anti-CD4 and intracellular anti-IL-17A monoclonal antibodies. IL-17+ cell proportions were analyzed in the CD4+ lymphocyte gate. We observed that patients at the time of hematologic reconstitution had higher proportions of IL-17-producing cells than healthy control subjects (0.73±0.13 vs 0.19±0.06%; P=.019). Fourteen patients displayed the first symptoms of aGvHD at the time of hematologic reconstitution, when they showed lower proportions of IL-17+ cells among CD4+ lymphocytes than their counterparts lacking aGvHD at a similar time after transplantation (0.29±0.09 vs 0.73±0.13%; P=.024). Eight patients developed aGvHD after hematologic reconstitution (median, 34 days). All of these patients displayed lower proportions of IL-17-producing CD4+ cells on the day of aGvHD compared with their initial measurements preceding this complication (0.34±0.14 vs 1.07±0.37%; P=.01).
白细胞介素 - 17A是称为辅助性T细胞17（T(H)17）的CD4 +淋巴细胞亚群的一个标志。异基因造血干细胞移植（HSCT）会引发一种有助于移植物接受的免疫反应，但如果临床表现为急性移植物抗宿主病（aGvHD），则可能会对移植结果产生不利影响。TH17细胞参与了与多种疾病相关的炎症过程，其中炎症性肠病（IBD）是典型代表。在本研究中，我们调查了HSCT术后患者外周血单个核细胞（PBMC）中产生IL - 17的细胞的存在情况。48例患者的中位年龄为45岁（范围1.0 - 64岁），患有血液系统恶性肿瘤（n = 45）或非恶性疾病（n = 3），接受了匹配的无关供者（n = 24）或同胞供者（n = 24）移植。我们检测了HSCT术后同种异体反应中产生IL - 17的细胞。在BD GolgiStop存在的情况下，用BD白细胞激活鸡尾酒（离子霉素、布雷菲德菌素A和佛波醇肉豆蔻酸酯（PMA））刺激PBMC。刺激后，细胞用抗CD4和细胞内抗IL - 17A单克隆抗体进行标记。在CD4 +淋巴细胞门中分析IL - 17 +细胞比例。我们观察到，血液学重建时患者产生IL - 17的细胞比例高于健康对照受试者（0.73±0.13对0.19±0.06%；P = 0.019）。14例患者在血液学重建时出现aGvHD的首发症状，此时他们CD4 +淋巴细胞中IL - 17 +细胞的比例低于移植后类似时间未发生aGvHD的患者（0.29±0.09对0.73±0.13%；P = 0.024）。8例患者在血液学重建后发生aGvHD（中位时间34天）。与发生这种并发症之前的初始测量值相比，所有这些患者在aGvHD发生当天产生IL - 17的CD4 +细胞比例均较低（0.34±0.14对1.07±0.37%；P = 0.01）。
