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Systemic Immunomodulatory Effects of Combinatorial Treatment of Thalidomide and Dexamethasone on T Cells and Other Immune Cells

Authors
 Eun Jee Kim  ;  Joon Ye Kim  ;  Hoon Young Choi  ;  Hyojung Lee  ;  Juhan Lee  ;  Myoung Soo Kim  ;  Yu Seun Kim  ;  Kyu Ha Huh  ;  Beom Seok Kim 
Citation
 YONSEI MEDICAL JOURNAL, Vol.62(2) : 137-148, 2021-02 
Journal Title
 YONSEI MEDICAL JOURNAL 
ISSN
 0513-5796 
Issue Date
2021-02
MeSH
Animals ; CTLA-4 Antigen / metabolism ; Cell Differentiation / drug effects ; Cell Proliferation / drug effects ; Dendritic Cells / drug effects ; Dendritic Cells / metabolism ; Dexamethasone / pharmacology* ; Flow Cytometry ; Immunomodulation / drug effects* ; Lymphocyte Activation / drug effects ; Lymphocyte Culture Test, Mixed ; Male ; Mice, Inbred C57BL ; Programmed Cell Death 1 Receptor / metabolism ; Spleen / cytology ; T-Lymphocytes / drug effects ; T-Lymphocytes / immunology* ; T-Lymphocytes, Regulatory / immunology ; Thalidomide / pharmacology*
Keywords
CTLA-4 antigen ; Immunomodulation ; T-lymphocytes ; dendritic cells ; dexamethasone ; thalidomide
Abstract
Purpose: In organ transplantation, the need for immune modulation rather than immune suppression has been emphasized. In this study, we investigated whether combinatorial treatments of with thalidomide (TM) and dexamethasone (DX) might be new approaches to induce systemic immunomodulation on T cells and other immune cells that regulate the expression of co-inhibitory molecules. Materials and methods: Naïve splenic T cells from C57BL/6 mice were sort-purified and cultured in vitro for CD4+ T cell proliferation and regulatory T cell (Treg) conversion in the presence of TM or/and DX. Expression of cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4) and programmed death-1 (PD-1) in proliferated and converted T cells was quantified by flow cytometry. We also quantified in vivo expression of CTLA-4 and PD-1 on splenic CD4+ T cells and other immune cells isolated from TM- or/and DX-treated mice. Mixed lymphocytes reactions (MLR) were performed to evaluate the capacity of immune cells in carrying out immune responses. Results: CTLA-4 expressions in effector T cells in vivo and in Tregs in vivo/vitro significantly increased upon TM/DX combinatorial treatment. Corresponding to increased CTLA-4 expression in T cells, the expression of ligand molecules for CTLA-4 significantly increased in splenic dendritic cells in TM/DX-treated groups. In addition, MLR results demonstrated that splenocytes isolated from TM/DX-treated mice significantly suppressed the proliferation of T cells isolated from other strains. Conclusion: Based on these results, we suggest that TM/DX combinatorial treatments might be efficient immunomodulatory methods for regulating T cell immunity.
DOI
10.3349/ymj.2021.62.2.137
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Surgery (외과학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Internal Medicine (내과학교실) > 1. Journal Papers
Yonsei Authors
Kim, Myoung Soo(김명수) ORCID logo https://orcid.org/0000-0002-8975-8381
Kim, Beom Seok(김범석) ORCID logo https://orcid.org/0000-0002-5732-2583
Kim, Yu Seun(김유선) ORCID logo https://orcid.org/0000-0002-5105-1567
Lee, Ju Han(이주한)
Choi, Hoon Young(최훈영) ORCID logo https://orcid.org/0000-0002-4245-0339
Huh, Kyu Ha(허규하) ORCID logo https://orcid.org/0000-0003-1364-6989
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/182106
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