Raja Karthick Raja Muthu, Plasil Martin, Rihova Lucie, Pelcova Jana, Adam Zdenek, Hajek Roman
Department of Pathological Physiology, Babak Myeloma Group, Faculty of Medicine, Masaryk University, Brno, Czech Republic; Department of Experimental Biology, Faculty of Science, Masaryk University, Brno, Czech Republic.
Cytometry B Clin Cytom. 2014 Jul;86(4):220-8. doi: 10.1002/cyto.b.21109. Epub 2013 Aug 6.
Multiple myeloma (MM) is a malignancy of plasma cells frequently associated with immune abnormalities. Several studies have confirmed that in MM immune deregulation can be mediated by increased numbers of CD4 T regulatory (Treg) cells, and these cells were also associated with poor outcome. In this study, we aimed to study CD8 Treg cells before and after lenalidomide plus dexamethasone (len-dex) treatment in MM patients.
Using flow cytometry, we enumerated and assessed suppressive function of CD8 Treg cells in 16 MM patients before and after len-dex treatment.
Numbers of CD8 Treg cells (CD8+CD25hi+FoxP3+) (P < 0.01) were significantly increased in MM patients (before treatment) compared to healthy donors. However, no significant changes were observed in CD4 and CD8 T cells. A significant increase in CD8 Treg cells was observed after len-dex treatment compared to pre-treatment but no significant difference was observed in CD4 and CD8 T cells. Proliferation assay data showed that CD8 Treg cells inhibited proliferation of CD4 T cells and IFN-γ secretion in a concentration dependent manner. Suppressive activity of CD8 Treg cells did not differ significantly between healthy donors, untreated and len-dex treated MM patients. A significant abnormal level of IL-10 was observed from proliferation assays of untreated and len-dex treated MM patients compared to healthy donors (P ≤ 0.03).
Using flow cytometry, we have shown that suppressive CD8 Treg cells are increased in MM patients and len-dex treatment is unable to control these suppressive CD8 Treg cells.
多发性骨髓瘤（MM）是一种浆细胞恶性肿瘤，常伴有免疫异常。多项研究证实，在MM中，免疫失调可由CD4调节性T（Treg）细胞数量增加介导，且这些细胞也与预后不良相关。在本研究中，我们旨在研究来那度胺联合地塞米松（来那度胺-地塞米松）治疗前后MM患者中的CD8 Treg细胞。
我们采用流式细胞术，对16例MM患者在来那度胺-地塞米松治疗前后的CD8 Treg细胞进行计数并评估其抑制功能。
与健康供者相比，MM患者（治疗前）的CD8 Treg细胞（CD8+CD25hi+FoxP3+）数量显著增加（P<0.01）。然而，CD4和CD8 T细胞未观察到显著变化。与治疗前相比，来那度胺-地塞米松治疗后CD8 Treg细胞显著增加，但CD4和CD8 T细胞未观察到显著差异。增殖试验数据显示，CD8 Treg细胞以浓度依赖性方式抑制CD4 T细胞增殖和IFN-γ分泌。健康供者、未经治疗和来那度胺-地塞米松治疗的MM患者之间，CD8 Treg细胞的抑制活性无显著差异。与健康供者相比，未经治疗和来那度胺-地塞米松治疗的MM患者增殖试验中IL-10水平显著异常（P≤0.03）。
通过流式细胞术，我们发现MM患者中抑制性CD8 Treg细胞增加，而来那度胺-地塞米松治疗无法控制这些抑制性CD8 Treg细胞。
