*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.

« Back to 2019 American Transplant Congress