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

Falk, Ingrid; Eichmann, Klaus

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

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Falk, Ingrid
Emeritus Group: Cellular Immunology, Max Planck Institute of Immunobiology and Epigenetics, Max Planck Society;

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Eichmann, Klaus
Department of Cellular and Molecular Immunology, Max Planck Institute of Immunobiology and Epigenetics, Max Planck Society;

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Citation

Falk, I., & Eichmann, K. (2002). Heterogeneity of the DN4 (CD44¯ CD25¯) subset of CD4¯ CD8¯ double negative thymocytes; dependence on CD3 signaling. Immunology Letters, 82(1-2 Sp. Iss. SI), 123-130.

Cite as: https://hdl.handle.net/11858/00-001M-0000-002B-9639-6

Abstract

Recent studies have shown that apoptotic cell death associated with selection for thymocytes that express clonotypic TCRβ or TCRγδ 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 CD3ε proteins we find that DN4 cells consist of five subpopulations: TCRβIC^high/CD3εIC^high/TCRγδIC¯, TCRβI-C¯/CD3εIC^high/TCRγδIC^₊, TCRβIC^high/CD3εIC^high/TCRγδIC^₊, TCRβIC^low/CD3εIC^low/TCRγδIC¯, and TCRβIC¯/CD3εIC¯/TCRγδIC¯. Expression levels of IC TCRβ/CD3ε, and of Thy1.2, CD2, and CD69 at the cell surface suggest that the TCRβIC^low/CD3εIC^low/TCRγδIC¯ subset harbors the direct precursors of DP cells, and is critical for life/death decisions in early thymic selection. TCRβ/CD3ε downregulation is less pronounced in DN4 and DP cells of mice deficient for CD3ζ or for p56^lck, suggesting that the dynamics of TCR protein regulation in the DN4 subset is dependent on CD3 signaling. (C) 2002 Elsevier Science B.V. All rights reserved.