CD4-CD8-双阴性胸腺细胞DN4（CD44-CD25-）亚群的异质性；对CD3信号的依赖性。

Heterogeneity of the DN4 (CD44-CD25-) subset of CD4-CD8- double negative thymocytes; dependence on CD3 signaling.

作者信息

Falk Ingrid, Eichmann Klaus

机构信息

Max-Planck-Institut für Immunbiologie, Freiburg, Germany.

出版信息

Immunol Lett. 2002 Jun 3;82(1-2):123-30. doi: 10.1016/s0165-2478(02)00027-5.

DOI:10.1016/s0165-2478(02)00027-5

PMID:12008043

Abstract

Recent studies have shown that apoptotic cell death associated with selection for thymocytes that express clonotypic TCRbeta or TCRgammadelta proteins takes place in the DN4 (CD44-CD25-) subset of CD4-CD8- double negative (DN) thymocytes. A detailed analysis of the DN4 subset is therefore of interest. Using intracellular (IC) staining for clonotypic TCR and CD3varepsilon proteins we find that DN4 cells consist of five subpopulations: TCRbetaIC(high)/CD3varepsilonIC(high)/TCRgammadeltaIC-, TCRbetaI-C-/CD3varepsilonIC(high)/TCRgammadeltaIC(+), TCRbetaIC(high)/CD3varepsilonIC(high)/TCRgammadeltaIC(+), TCRbetaIC(low)/CD3varepsilonIC(low)/TCRgammadeltaIC(-), and TCRbetaIC(-)/CD3varepsilonIC(-)/TCRgammadeltaIC(-). Expression levels of IC TCRbeta/CD3varepsilon, and of Thy1.2, CD2, and CD69 at the cell surface suggest that the TCRbetaIC(low)/CD3varepsilonIC(low)/TCRgammadeltaIC(-) subset harbors the direct precursors of DP cells, and is critical for life/death decisions in early thymic selection. TCRbeta/CD3varepsilon downregulation is less pronounced in DN4 and DP cells of mice deficient for CD3zeta or for p56(lck), suggesting that the dynamics of TCR protein regulation in the DN4 subset is dependent on CD3 signaling.

摘要

最近的研究表明，与表达克隆型TCRβ或TCRγδ蛋白的胸腺细胞选择相关的凋亡性细胞死亡发生在CD4⁻CD8⁻双阴性（DN）胸腺细胞的DN4（CD44⁻CD25⁻）亚群中。因此，对DN4亚群进行详细分析很有意义。通过对克隆型TCR和CD3ε蛋白进行细胞内（IC）染色，我们发现DN4细胞由五个亚群组成：TCRβIC(高)/CD3εIC(高)/TCRγδIC⁻、TCRβI-C⁻/CD3εIC(高)/TCRγδIC(+)、TCRβIC(高)/CD3εIC(高)/TCRγδIC(+)、TCRβIC(低)/CD3εIC(低)/TCRγδIC⁻以及TCRβIC(⁻)/CD3εIC(⁻)/TCRγδIC(⁻)。细胞表面IC TCRβ/CD3ε以及Thy1.2、CD2和CD69的表达水平表明，TCRβIC(低)/CD3εIC(低)/TCRγδIC⁻亚群包含双阳性（DP）细胞的直接前体，并且对早期胸腺细胞选择中的生死决定至关重要。在缺乏CD3ζ或p56(lck)的小鼠的DN4和DP细胞中，TCRβ/CD3ε的下调不太明显，这表明DN4亚群中TCR蛋白调节的动态过程依赖于CD3信号传导。