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The Immunomodulating Effects of Thalidomide and Dexamethasone in a Murine Cardiac Allograft Transplantation Model

Authors
 Soo Jin Kim  ;  Joon Ye Kim  ;  Eun Jee Kim  ;  Hyojung Lee  ;  Yuri Cho  ;  Myoung Soo Kim  ;  Yu Seun Kim  ;  Beom Seok Kim  ;  Kyu Ha Huh 
Citation
 YONSEI MEDICAL JOURNAL, Vol.63(2) : 158-165, 2022-02 
Journal Title
YONSEI MEDICAL JOURNAL
ISSN
 0513-5796 
Issue Date
2022-02
MeSH
Allografts ; Animals ; Dexamethasone ; Graft Rejection / drug therapy ; Graft Rejection / prevention & control ; Graft Survival ; Leukocytes, Mononuclear* ; Mice ; Mice, Inbred C57BL ; T-Lymphocytes, Regulatory ; Thalidomide* / therapeutic use
Keywords
Immunomodulation ; T cells ; cardiac transplantation ; dendritic cells ; dexamethasone ; thalidomide
Abstract
Purpose: The immunomodulatory effects of thalidomide (TM) and dexamethasone (DX) on immune cells and their co-stimulatory, co-inhibitory molecules in vitro and in vivo have been previously reported. The current study investigated the effects of TM and the combinatorial treatment with DX on immune cells using a murine cardiac allograft transplantation model.

Materials and methods: Intraabdominal transplant of cardiac allografts from BALB/c (H-2d) donors to C57BL/6 (H-2b) recipients was performed. After transplantation, mice were injected daily with TM or DX or a combination of both TM and DX (TM/DX) by intraperitoneal route until the time of graft loss. CD4+ T cell subsets and CD11c+ cells in the peripheral blood mononuclear cells and spleen were examined and quantified with flow cytometry. Serum IL-6 levels were measured by enzyme-linked immunosorbent assay on day 7.

Results: The mean graft survivals were 6.86 days in the untreated group, and 10.0 days in the TM/DX group (p<0.001). The TM/DX treatment affected the CD4+ T cell subsets without suppressing the total CD4+ T cell population. The CD4+FOXP3+/CD4+CD44hi T cell ratio increased. Increase in cell counts and median fluorescence intensity on CD11c+CD85k+ with TM/DX were observed. The inhibition of pro-inflammatory cytokine interleukin-6 was also observed.

Conclusion: These outcomes suggest the immunomodulating effect of the TM/DX combinatorial treatment. In conclusion, TM/DX combination may be a promising immunomodulatory approach for preventing allograft rejection and improving graft survival by inducing tolerance in transplantation.
Files in This Item:
T202200435.pdf Download
DOI
10.3349/ymj.2022.63.2.158
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Internal Medicine (내과학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Surgery (외과학교실) > 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, Soo Jin(김수진)
Kim, Yu Seun(김유선) ORCID logo https://orcid.org/0000-0002-5105-1567
Huh, Kyu Ha(허규하) ORCID logo https://orcid.org/0000-0003-1364-6989
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/188017
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