Flow Cytometry-Based Enumeration and Functional Characterization of CD8 T Regulatory Cells in Patients with Multiple Myeloma Before and After Lenalidomide Plus Dexamethasone Treatment

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Title in English Flow Cytometry-Based Enumeration and Functional Characterization of CD8 T Regulatory Cells in Patients with Multiple Myeloma Before and After Lenalidomide Plus Dexamethasone treatment
Authors

MUTHU RAJA Karthick Raja PLÁŠIL Martin ŘÍHOVÁ Lucie PELCOVÁ Jana ADAM Zdeněk HÁJEK Roman

Year of publication 2014
Type Article in Periodical
Magazine / Source Cytometry Part B ( Clinical cytometry)
MU Faculty or unit

Faculty of Medicine

Citation
Doi http://dx.doi.org/10.1002/cyto.b.21109
Field Oncology and hematology
Keywords CD8 T regulatory cells; multiple myeloma; immune suppression; lenalidomide; dexamethasone; flow cytometry and CFSE
Attached files
Description Background: 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. Methods: Using flow cytometry, we enumerated and assessed suppressive function of CD8 Treg cells in 16 MM patients before and after len-dex treatment. Results: 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-gamma 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). Conclusions: 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. (C) 2013 International Clinical Cytometry Society
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