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Enhanced immune-modulatory effects of thalidomide and dexamethasone co-treatment on T cell subsets

 Eun Jee Kim  ;  Jae Geun Lee  ;  Joon Ye Kim  ;  Seung Hwan Song  ;  Dong Jin Joo  ;  Kyu Ha Huh  ;  Myoung Soo Kim  ;  Beom Seok Kim  ;  Yu Seun Kim 
 Immunology, Vol.152(4) : 628-637, 2017 
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Issue Date
4-1BB Ligand/immunology ; Animals ; Cell Proliferation/drug effects* ; Dexamethasone/pharmacology* ; Glucocorticoid-Induced TNFR-Related Protein/immunology ; Immunologic Factors/pharmacokinetics* ; Male ; Mice ; Receptors, OX40/immunology ; T-Lymphocyte Subsets/cytology ; T-Lymphocyte Subsets/immunology* ; T-Lymphocytes, Regulatory/cytology ; T-Lymphocytes, Regulatory/immunology* ; Thalidomide/pharmacology*
4-1BB ; OX40 ; T lymphocyte ; glucocorticoid-induced tumour necrosis factor receptor-related protein ; thalidomide
Thalidomide (TM) has been reported to have anti-cancer and anti-inflammatory properties, and dexamethasone (DX) is known to reduce inflammation and inhibit production of inflammatory cytokines. Many studies have reported that combinatorial therapy with TM and DX is clinically used to treat multiple myeloma and lupus nephritis, but the mechanism responsible for its effects has not been elucidated. In this study, we determined that TM and DX co-treatment had an enhanced immune-modulatory effect on T cells through regulating the expression of co-stimulatory molecules. Splenic naive T cells from C57BL/6 mice were sort-purified and cultured for CD4+ T cell proliferation and regulatory T (Treg) cell conversion in the presence of TM and/or DX. Following incubation with the drugs, cells were collected and OX40, 4-1BB, and glucocorticoid-induced tumour necrosis factor receptor-related protein (GITR) expression was quantified by flow cytometry. TM (1 or 10 μm) decreased CD4+ T cell proliferation in a dose-dependent manner, whereas TM/DX (0·1 or 1 nm) co-treatment further decreased proliferation. Treg cell populations were preserved following drug treatment. Furthermore, expression of co-stimulatory molecules decreased upon TM/DX co-treatment in effector T (Teff) cells and was preserved in Treg cells. Splenic CD4+ T cells isolated from TM- and DX-treated mice exhibited the same patterns of Teff and Treg cell populations as observed in vitro. Considering the selective effect of TM on different T cell subsets, we suggest that TM may play an immunomodulatory role and that TM/DX combinatorial treatment could further enhance these immunomodulatory effects by regulating GITR, OX40, and 4-1BB expression in CD4+ T cells.
Appears in Collections:
1. Journal Papers (연구논문) > 1. College of Medicine (의과대학) > Dept. of Internal Medicine (내과학교실)
1. Journal Papers (연구논문) > 1. College of Medicine (의과대학) > Dept. of Surgery (외과학교실)
Yonsei Authors
김명수(Kim, Myoung Soo) ; 김범석(Kim, Beom Seok) ; 김유선(Kim, Yu Seun) ; 이재근(Lee, Jae Geun) ; 주동진(Joo, Dong Jin) ; 허규하(Huh, Kyu Ha)
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