Role of Thalidomide on the Expression of OX40, 4-1BB, and GITR in T Cell Subsets

• Thalidomide downregulates OX40, 4-1BB, and GITR expression of effector T cells.
• On Treg conversion, OX40 was downregulated, and GITR was upregulated.
• Role of Thalidomide on the expressions of TNFRSFs differs in each T-cell subsets.

BackgroundThalidomide (TM) is known to have anti-cancer and anti-inflammatory properties; however, its mechanism on T cells is still unclear. We previously showed the immune modulatory effect of TM on T cells and its therapeutic effect on lupus nephritis models. Here we examined the changes in the expression of tumor necrosis factor receptor superfamilies (TNFRSFs), including OX40, 4-1BB, and glucocorticoid-induced TNFR-related protein (GITR) in T cell subsets by TM treatments.MethodsSplenic naïve T cells (Tnaives) from C57BL/6 mice were sort-purified and cultured for CD4+ T cell proliferation and regulatory T cells (Tregs) conversion with TM treatments. All samples were analyzed by flow cytometry after stained with anti-mouse CD4, Foxp3, OX40, 4-1BB, or GITR antibodies.ResultsExpressions of OX40, 4-1BB, and GITR on CD4+ T cells showed a decreasing tendency by TM treatments. Especially, downregulation of these molecules on CD4+CFSElow T cells was significant in TM treatment groups. On the condition of Treg conversion, OX40 was downregulated significantly. In contrast, the expression of GITR was increased, and that of 4-1BB had shown no particular change under the condition of Treg.ConclusionConsidering these results, TM may have an immune modulatory role through the T cell subset-specific change of OX40, 4-1BB, and GITR expression. Further study is required to elucidate the effect of thalidomide on T cells.