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

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.

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

“…Previously, we reported on the effects of TM and DX on immune cells and their co-stimulatory, co-inhibitory molecules in vitro and in vivo. 28 29 30 31 This study utilises a murine cardiac transplant model to verify our preceding findings and elucidate the immunomodulating affinity of TM. As previously described, TM/DX treatment affected CD4 + T cell subsets by down-regulating Teffs while preserving Tregs in both in vitro.…”

“…Due to this interrelation, we demonstrated the inhibitory functions of TM/DX treated DCs on T cell proliferation by performing mixed lymphocyte reactions in a previous study. 31 In this mouse cardiac transplantation model, CD11c + cell population (DCs) increased after transplantation but showed no difference in cell frequency regardless of drug treatment ( Fig. 3 ).…”

“…4 ), the MFI of the CD85k + significantly increased with TM/DX treatment in both PBMC and spleen, in contrast to DX alone, comparable to our previous results. 31 CD85k (ILT3), an immunoglobulin-like transcript (ILT), is one of the biomarkers expressed on tolerogenic CD11c + cells, and an enhanced expression of CD11c + cells with TM/DX combination may indicate the induction of tolerogenic characteristics of DCs. 33 Tregs are developed in the thymus and extrathymic sites, such as secondary lymphoid organs (SLOs).…”

“… 28 Co-treatment of TM and DX (TM/DX) increased cytotoxic T lymphocyte associated antigen-4 expression in CD4 + Teffs and CD4 + Tregs and increased the corresponding ligands (CD80, CD86) of DCs, suggesting the activation of DC-mediated tolerance effects. 29 30 31 The competency of TM/DX combinatorial treatments for maintaining a tolerogenic state or immune homeostasis was suggested.…”

Effects of Biopolymers from Cassava Implanted with Rodent Bait on Wistar Rats

“…However, the bait meal and 6.0 g zinc phosphide category (70.67%), the white blood cell counts showed the presence of an inflammation and certain levels of tissue damage. WBCs are involved in the cellular and humoral defense of the organism against foreign material [36][37][38]. Increase in the level of white blood cell counts is common where there is prolonged exposure to potentially toxic agent or persistence of an injurious agent.…”