Yonsei Med J.  2021 Feb;62(2):137-148. 10.3349/ymj.2021.62.2.137.

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

Affiliations
  • 1The Research Institute for Transplantation, Yonsei University College of Medicine, Seoul, Korea.
  • 2Brain Korea 21 PLUS Project for Medical Science, Yonsei University, Seoul, Korea.
  • 3Division of Nephrology, Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea.
  • 4Department of Transplantation Surgery, Yonsei University College of Medicine, Seoul, Korea.

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.

Keyword

Immunomodulation; thalidomide; dexamethasone; CTLA-4 antigen; T-lymphocytes; dendritic cells
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