Mpakou Vassiliki E, Ioannidou Heleni-Dikaia, Konsta Eugene, Vikentiou Myrofora, Spathis Aris, Kontsioti Frieda, Kontos Christos K, Velentzas Athanassios D, Papageorgiou Sotiris, Vasilatou Diamantina, Gkontopoulos Konstantinos, Glezou Irene, Stavroulaki Georgia, Mpazani Efthimia, Kokkori Stella, Kyriakou Elias, Karakitsos Petros, Dimitriadis George, Pappa Vasiliki
Second Dept. of Internal Medicine and Research Institute, Attikon University Hospital, 1 Rimini st., Haidari, Athens, 12462, Greece.
Department of Cytopathology, Attikon University Hospital, Athens, Greece.
Leuk Res. 2017 Sep;60:74-81. doi: 10.1016/j.leukres.2017.07.004. Epub 2017 Jul 25.
Accumulated data indicate a significant role of T cell dysfunction in the pathogenesis of chronic lymphocytic leukemia. In CLL, regulatory T cells are significantly higher and show lower apoptotic levels compared to healthy donors. We demonstrate that CLL derived CD4CD25CD127 and CD4CD25CD127 subpopulations share a common immunophenotypic profile with conventional Tregs and are associated with advanced stage disease. We further provide evidence that the increased number of Tregs contributes indirectly to the proliferation of the CLL clone, by suppressing the proliferation of Teffs which in turn suppress CLL cells. These data are further supported by our observations that CLL derived Tregs appear rather incapable of inducing apoptosis of both normal B cells and CLL cells, in contrast to normal Tregs, suggesting an immunoediting effect of CLL cells on Tregs which negatively affects the functionality of the latter and contributes to the failure of Tregs in CLL to efficiently eliminate the abnormal clone.
累积数据表明T细胞功能障碍在慢性淋巴细胞白血病的发病机制中起重要作用。在慢性淋巴细胞白血病中，与健康供体相比，调节性T细胞显著增多且凋亡水平较低。我们证明，慢性淋巴细胞白血病来源的CD4CD25CD127和CD4CD25CD127亚群与传统调节性T细胞具有共同的免疫表型特征，且与疾病晚期相关。我们进一步提供证据表明，调节性T细胞数量的增加通过抑制效应T细胞（Teffs）的增殖间接促进慢性淋巴细胞白血病克隆的增殖，而效应T细胞反过来又抑制慢性淋巴细胞白血病细胞。我们的观察结果进一步支持了这些数据，即与正常调节性T细胞相比，慢性淋巴细胞白血病来源的调节性T细胞似乎相当无法诱导正常B细胞和慢性淋巴细胞白血病细胞凋亡，这表明慢性淋巴细胞白血病细胞对调节性T细胞有免疫编辑作用，对后者的功能产生负面影响，并导致慢性淋巴细胞白血病中调节性T细胞无法有效清除异常克隆。
