Thalidomide (TM) is known to have anti-inflammatory effects and dexamethasone (DX) is also well known to reduce inflammation and inhibit inflammatory cytokine production. Clinically, combinatorial therapy of TM and DX is widely used in treatment for multiple myeloma with proven efficacy. Our previous studies have shown that TM/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. In this study, we determined the effect of TM/DX combinatorial treatments on other immune cell types isolated from murine splenocytes.

Spleens were isolated from eight-week-old normal C57BL/6 mice received chow containing either no drug, TM, DX, or TM/DX for one week. Homogenized splenocytes were then stained with PE-Cy7-conjugated anti-mouse CD8, PerCP-Cy-5.5-conjugated anti-mouse CD19, and PerCP-Cy5.5-conjugated anti-mouse CD11c antibodies and the population of CD8⁺ T cells, CD19⁺ B cells, and CD11c⁺ dendritic cells (DCs) were quantified by flow cytometry.

CD8⁺ T cell population was significantly increased in DX and TM/DX groups, which we attribute to the effect of DX. CD19⁺ cell population, however, showed the exact opposite results that it significantly decreased in DX and TM/DX groups, which also resulted from the effect of DX. DC population was slightly increased upon DX, but upon TM/DX combinatorial treatment, DC population was increased about two-fold compared to that of CTL, TM, and DX groups.

Considering the results, we suggest that TM/DX combinatorial treatment plays enhanced immune-modulatory role by having the varying effects on different immune cells. Compared to immunosuppressant drugs, which reduce 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. Further study will be conducted, mainly focusing on the drug effect on DCs, to determine the underlying molecular links between the TM/DX's effects and immune cells.

CITATION INFORMATION: Kim E., Kim J., Huh K., Cho Y., Kim M., Kim Y., Kim B. Immune Modulatory Effect of Thalidomide and Dexamethasone Co-Treatment on Murine Splenocytes Am J Transplant. 2017;17 (suppl 3).

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