Kim B S, Kim J Y, Kim E J, Lee J G, Joo D J, Huh K H, Kim M S, Kim Y S
The Research Institute for Transplantation, Yonsei University College of Medicine Seoul, Republic of Korea; Division of Nephrology, Department of Internal Medicine Severance Hospital, Yonsei University Health System, Seoul, Republic of Korea.
The Research Institute for Transplantation, Yonsei University College of Medicine Seoul, Republic of Korea.
Transplant Proc. 2016 May;48(4):1270-4. doi: 10.1016/j.transproceed.2015.12.088.
Thalidomide (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.
Splenic 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.
Expressions of OX40, 4-1BB, and GITR on CD4(+) T cells showed a decreasing tendency by TM treatments. Especially, downregulation of these molecules on CD4(+)CFSE(low) 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.
Considering 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.
沙利度胺（TM）具有抗癌和抗炎特性；然而，其对T细胞的作用机制仍不清楚。我们之前展示了TM对T细胞的免疫调节作用及其对狼疮性肾炎模型的治疗效果。在此，我们通过TM处理研究了肿瘤坏死因子受体超家族（TNFRSFs），包括OX40、4-1BB和糖皮质激素诱导的TNFR相关蛋白（GITR）在T细胞亚群中表达的变化。
对C57BL/6小鼠的脾脏初始T细胞（Tnaives）进行分选纯化，并通过TM处理培养以促进CD4(+) T细胞增殖和调节性T细胞（Tregs）转化。用抗小鼠CD4、Foxp3、OX40、4-1BB或GITR抗体染色后，所有样本通过流式细胞术进行分析。
通过TM处理，CD4(+) T细胞上OX40、4-1BB和GITR的表达呈下降趋势。特别是，在TM处理组中，CD4(+)CFSE(low) T细胞上这些分子的下调显著。在Treg转化条件下，OX40显著下调。相反，在Treg条件下，GITR的表达增加，而4-1BB的表达没有特别变化。
考虑到这些结果，TM可能通过OX40、4-1BB和GITR表达的T细胞亚群特异性变化发挥免疫调节作用。需要进一步研究以阐明沙利度胺对T细胞的作用。
