T cell-expressed Ift88 is required for proper thymocyte differentiation in mice

小鼠胸腺细胞分化需要T细胞表达的Ift88。

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作者:Sarah J Miller ,Nancy M Gonzalez ,Morgan E Smith ,Mandy J Croyle ,Bradley K Yoder ,Kurt A Zimmerman

Abstract

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.

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