Cukrová Vera, Neuwirtová Radana, Dolezalová Ludmila, Belicková Monika, Bartůnková Jirina, Jonásová Anna, Cermák Jaroslav, Homolková Hana, Malíková Ivana
1st Medical Clinic Charles University, Prague, Czech Republic.
Exp Hematol. 2009 Mar;37(3):386-94. doi: 10.1016/j.exphem.2008.11.001. Epub 2009 Jan 10.
The capacity of mononuclear blood cells to form autoreactive cytotoxic T lymphocytes was investigated in order to elucidate the mechanism of successful immunosuppressive therapy in some myelodysplastic syndrome (MDS) patients (autoreactivity studies). The failure in autoreactivity studies raised the question of alloreactive cytotoxic T lymphocyte formation in MDS (alloreactivity studies).
Sixteen MDS patients and relevant controls were examined. Autoreactive lymphocytes directed against autologous bone marrow mononuclear cells and alloreactive lymphocytes directed against unrelated third-party cells were tested using cytotoxicity assay. In addition, we used one-way mixed lymphocyte reaction, human androgen receptor test for clonality detection, and enzyme-linked immunosorbent assay kits for tumor necrosis factor and interferon-gamma testing.
We did not confirm the presence of autoreactive T cells in eight of nine MDS patients tested. The response to allogeneic cells was impaired in 11 of 16 MDS patients, more often in refractory anemia (RA; 80%) than in RA with ring sideroblasts (40%). Interestingly, the response to allogeneic cells in mixed lymphocyte reaction was normal in all MDS patients. T lymphocytes were polyclonal in all but one patient. Tumor necrosis factor and interferon-gamma level in supernatants of mononuclear cells was significantly reduced in RA.
The presumed autoaggressive T cells were not confirmed in MDS in our experimental arrangement. Alloreactivity studies demonstrated the impairment of effector cytotoxic phase of cell-mediated immunological reaction in MDS, namely in RA. The significance of our finding of defective cytotoxicity for pathogenesis, clinical course, and even for therapy is discussed together with other immunological defects reported so far.
研究单核血细胞形成自身反应性细胞毒性T淋巴细胞的能力，以阐明某些骨髓增生异常综合征（MDS）患者免疫抑制治疗成功的机制（自身反应性研究）。自身反应性研究的失败引发了MDS中同种异体反应性细胞毒性T淋巴细胞形成的问题（同种异体反应性研究）。
检查了16例MDS患者及相关对照。使用细胞毒性试验检测针对自体骨髓单核细胞的自身反应性淋巴细胞和针对无关第三方细胞的同种异体反应性淋巴细胞。此外，我们使用单向混合淋巴细胞反应、人雄激素受体试验进行克隆性检测，以及酶联免疫吸附测定试剂盒检测肿瘤坏死因子和干扰素-γ。
在检测的9例MDS患者中，有8例未证实存在自身反应性T细胞。16例MDS患者中有11例对异基因细胞的反应受损，难治性贫血（RA；80%）比伴有环形铁粒幼细胞的RA（40%）更常见。有趣的是，所有MDS患者在混合淋巴细胞反应中对异基因细胞的反应均正常。除1例患者外，所有患者的T淋巴细胞均为多克隆性。RA患者单核细胞上清液中的肿瘤坏死因子和干扰素-γ水平显著降低。
在我们的实验安排中，MDS中未证实存在推测的自身攻击性T细胞。同种异体反应性研究表明，MDS中细胞介导的免疫反应效应细胞毒性阶段受损，即在RA中受损。我们发现的细胞毒性缺陷对发病机制、临床病程甚至治疗的意义，与迄今为止报道的其他免疫缺陷一起进行了讨论。
