Characterization of an Expanded IL-10-Producing-Suppressive T Cell Population Associated with Immune Tolerance
Characterization of an Expanded IL-10-Producing-Suppressive T Cell Population Associated with Immune Tolerance
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DOI：
10.1248/bpb.b19-01072
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发表时间：
2021-04-01
影响因子：
2
通讯作者：
Kohno, Takeyuki
中科院分区：
文献类型：
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作者：
Yoshida, Yuya;Mikami, Norihisa;Kohno, Takeyuki
用芬戈莫德（FTY 720）治疗关节炎小鼠模型后，糖皮质激素诱导的肿瘤坏死因子受体家族相关基因/蛋白（GITR）（+）CD 25（-）（或叉头盒蛋白3：Foxp 3（-））CD 4（+）T细胞数量的增加和致病抗原可能在免疫耐受的建立中起关键作用。在这项研究中，我们的特点是一个特定的扩展T细胞亚群在这个群体中。用FTY 720（1 mg/ kg，口服）和GPI（325-339）（10 μ g/小鼠，静脉内）治疗患有葡萄糖-6-磷酸异构酶肽（GPI（325 - 339））诱导的关节炎的小鼠5天，从症状发作开始。使用流式细胞术检查扩增的GITR（+）CD 25（-）（或Foxp 3（-））CD 4（+）T细胞群及其细胞因子产生。此外，检查了该T细胞亚群中T-bet和/或早期生长反应基因2（Egr-2）表达的时间依赖性变化。与未处理组和单处理组相比，仅在联合处理组中，GITR（+）Foxp 3（-）CD 4（+）T细胞群中具有免疫球蛋白（IG）和基于免疫受体酪氨酸的抑制基序结构域（TIGIT）（+）CD 39（+）细胞亚群的T细胞免疫受体密度显著增加。在TIGIT（+）CD 39（+）GITR（+）Foxp 3（-）CD 4（+）T细胞群中，T-bet（+）Egr-2（+）/T-bet（+）Egr-2（-）细胞比率在治疗后期增加。此外，该T细胞亚群对应于辅助性T细胞1（Th 1）应答，产生高水平的白细胞介素（IL）-10和干扰素（IFN）-γ。总之，扩增的TIGIT（+）CD 39（+）GITR（+）Foxp 3（-）CD 4（+）T细胞从效应Th 1转变为产生IL-10的抑制性T细胞表型，这可能促进免疫耐受状态。
An increase in the number of glucocorticoid-induced tumor necrosis factor receptor-family related gene/ protein (GITR)(+)CD25(-) (or fork-head box protein 3: Foxp3(-)) CD4(+) T cells, after treating a mouse model of arthritis with fingolimod (FTY720), and a pathogenic antigen may play a key role in the establishment of immune tolerance. In this study, we characterized a specific expanded T cell subset in this population. Mice with glucose-6-phosphate isomerase peptide (GPI(325-339))-induced arthritis were treated with FTY720 (1 mg/ kg, per os) and GPI(325-339) (10 mu g/mouse, intravenously) for five days, starting from the onset of symptoms. The expanded GITR(+)CD25(-) (or Foxp3(-)) CD4(+) T cell population and its cytokine production were examined using flow cytometry. Furthermore, time-dependent changes in T-bet and/or early growth response gene 2 (Egr-2) expression in this T cell subset were examined. The density of T cell immunoreceptors with immunoglobulin (Ig) and immunoreceptor tyrosine-based inhibition motif domains (TIGIT)(+)CD39(+) cell subset in the GITR(+)Foxp3(-) CD4(+) T cell population was significantly increased only in the combined treatment group, compared to that in the untreated and single-treatment groups. In the TIGIT(+)CD39(+) GITR(+) Foxp3(-) CD4(+) T cell population, T-bet(+)Egr-2(+)/T-bet(+)Egr-2(-) cell ratio increased in the latter stage of the treatment. Furthermore, this T cell subset, which corresponded to a T helper 1 (Th1) response, produced high levels of both interleukin (IL)-10 and interferon (IFN)-gamma. In conclusion, expanded TIGIT(+)CD39(+) GITR(+)Foxp3(-)CD4(+) T cells shifted from an effector Th1 to IL-10-producing-suppressor T cell phenotype, which may promote an immune-tolerant state.