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Enhanced immune‐modulatory effects of thalidomide and dexamethasone co‐treatment on T cell subsets
Author(s) -
Kim Eun Jee,
Lee Jae Geun,
Kim Joon Ye,
Song Seung Hwan,
Joo Dong Jin,
Huh Kyu Ha,
Kim Myoung Soo,
Kim Beom Seok,
Kim Yu Seun
Publication year - 2017
Publication title -
immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.297
H-Index - 133
eISSN - 1365-2567
pISSN - 0019-2805
DOI - 10.1111/imm.12804
Subject(s) - flow cytometry , t cell , immune system , cytotoxic t cell , dexamethasone , thalidomide , cell growth , cell , immunology , chemistry , biology , cancer research , pharmacology , microbiology and biotechnology , medicine , in vitro , multiple myeloma , endocrinology , biochemistry
Summary 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 C57 BL /6 mice were sort‐purified and cultured for CD 4 + 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 OX 40, 4‐1 BB , and glucocorticoid‐induced tumour necrosis factor receptor‐related protein ( GITR ) expression was quantified by flow cytometry. TM (1 or 10 μ m ) decreased CD 4 + T cell proliferation in a dose‐dependent manner, whereas TM / DX (0·1 or 1 n m ) 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 CD 4 + 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 , OX 40, and 4‐1 BB expression in CD 4 + T cells.