Sarah J Miller, Nancy M Gonzalez, Morgan E Smith, Mandy J Croyle, Bradley K Yoder, Kurt A Zimmerman
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引用次数: 0
摘要
胸腺纤毛的形成和非纤毛依赖性功能(包括 T 细胞免疫突触的形成)需要鞘内转运蛋白 88(Ift88)。为了测试 Ift88 在 T 细胞发育中的作用,我们对胸腺上皮细胞(TECs)或 T 细胞中缺乏 Ift88 的小鼠分离出的胸腺和脾脏组织进行了流式细胞术分析。分析表明,TEC Ift88 缺失对胸腺 T 细胞的发育没有影响,对脾脏 T 细胞的影响很小。对 CaggCreERT2+Ift88 tm1BkymTmG 小鼠 T 细胞的分析表明,在他莫昔芬诱导后 3 周,大约一半的 DN1 胸腺细胞缺乏 Ift88;Ift88 缺失不会影响 DN2-DN4 阶段或 CD4+/CD8+ 双阳性 (DP) 胸腺细胞阶段的 T 细胞发育。然而,缺失 Ift88 的 T 细胞在单阳性(SP)胸腺细胞阶段的存活率明显降低,脾脏和肾脏中 CD4+ 和 CD8+ T 细胞的数量也是如此。尽管Ift88缺陷细胞优先存活,但脾脏和肾脏中的T细胞总数受Ift88缺失的影响很小。这些数据表明,DP胸腺细胞分化成SP胸腺细胞需要Ift88,而Ift88熟练的T细胞可以补偿缺乏的细胞,以填补开放的龛位。
T cell-expressed Ift88 is required for proper thymocyte differentiation in mice.
Intraflagellar transport protein 88 (Ift88) is required for the formation of cilia in the thymus and non-ciliary dependent functions including T cell immune synapse formation. To test the role of Ift88 in T cell development, we performed flow cytometry analysis on thymus and spleen tissue isolated from mice lacking Ift88 in thymic epithelial cells (TECs) or T cells. Analyses indicated that TEC Ift88 deletion had no impact on thymic T cell development and minimal impact on splenic T cells. Analysis of T cells in CaggCreERT2+Ift88 tm1BkymTmG mice indicate that approximately half of DN1 thymocytes are Ift88 deficient 3 weeks post-tamoxifen induction; Ift88 loss did not impact T cell development at the DN2-DN4 stage or the CD4+/CD8+ double-positive (DP) thymocyte stage. However, survival of Ift88 deficient T cells was significantly reduced at the single-positive (SP) thymocyte stage, as was the number of CD4+ and CD8+ T cells in spleen and kidney. Despite preferential survival of Ift88-proficient cells, the total number of T cells the in spleen and kidney was minimally impacted by Ift88 loss. These data suggest Ift88 is required for differentiation of DP thymocytes into SP thymocytes and that Ift88 proficient T cells can compensate for deficient cells to fill the open niche.
期刊介绍:
Physiological Reports is an online only, open access journal that will publish peer reviewed research across all areas of basic, translational, and clinical physiology and allied disciplines. Physiological Reports is a collaboration between The Physiological Society and the American Physiological Society, and is therefore in a unique position to serve the international physiology community through quick time to publication while upholding a quality standard of sound research that constitutes a useful contribution to the field.