Date: Monday, June 3, 2019
Session Name: Poster Session C: Immunosuppression Preclinical Studies
Session Time: 6:00pm-7:00pm
Presentation Time: 6:00pm-7:00pm
Location: Hall C & D
*Purpose: Thalidomide (TM) is known to have anti-cancer and anti-inflammatory effects and dexamethasone (DX) has been reported that it also reduces inflammation and inhibits inflammatory cytokine production. We also have shown that TM and DX combinatorial treatments have immune-modulatory functions and affect each CD4+ T cell subset differently and specifically, by regulating the expression of co-stimulatory molecules on CD4+ T cells. Therefore, in this study, we examined TM/DX combinatorial effects on CD8+ T cells to compare CD4+ and CD8+ T cells.
*Methods: Splenic CD8+ T lymphocytes isolated from C57BL/6 mice were cultured for proliferation with anti-CD3 and CD28 antibodies for 72 h, and Cell Trace violet dye (CTV) labeling method was used for measuring of proliferation. Sort purified CD8+ T cells were plated at 1.5 × 105 cells on 96-well plates with thalidomide or/and dexamethasone. Following incubation with the drugs, cells were collected and OX40, glucocorticoid-induced tumour necrosis factor receptor-related protein (GITR), programmed cell death-1 (PD-1), and cytotoxic T lymphocyte associated antigen-4 (CTLA-4) expression was quantified by flow cytometry.
*Results: TM significantly decreased the viability of CD8+ T cells in a dose-dependent manner (P<.02) and showed synergistic effect on lowering CD8+ T population when combined with low dose of dexamethasone (P<.03). The proliferation of CD8+ T cells was not changed significantly upon the drug treatments. Compared to the TM single treatments, TM/DX combinational treatments further decrease the expression of co-stimulatory molecules, GITR and OX40, which were required for CD8+ T cell expansion or enhancement of its function. The expression of inhibitory molecules, PD-1 and CTLA-4, was not significantly changed by TM/DX treatments.
*Conclusions: Considering the results and the CD4+ T cell data we previously reported, we suggest that TM/DX combinatorial treatment plays enhanced immune-modulatory role by selectively suppressing CD4+ effector T cell proliferation and CD8+ T cell viability. Compared to immunosuppressant drugs, which generally reduce T cell and immune cell populations regardless of their subsets or types, TM/DX combinatorial treatment showed clear modulating effects and can be potentially used as a viable immune-modulatory therapy following transplantation.
To cite this abstract in AMA style:Kim J, Kim E, Cho Y, Lee H, Kim M, Kim Y, Huh K, Kim B. Effects of Thalidomide and Dexamethasone Co-Treatment on CD8+ T Cells [abstract]. Am J Transplant. 2019; 19 (suppl 3). https://atcmeetingabstracts.com/abstract/effects-of-thalidomide-and-dexamethasone-co-treatment-on-cd8-t-cells/. Accessed April 14, 2021.
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