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Cross-linking of T-cell receptors on double-positive thymocytes induces a cytokine-mediated stromal activation process linked to cell death.

1996; Springer Nature; Volume: 15; Issue: 21 Linguagem: Inglês

10.1002/j.1460-2075.1996.tb00974.x

1460-2075

Adam Lerner, Linda K. Clayton, Emiko Mizoguchi, Yoseph Ghendler, Willem van Ewijk, Shigeo Koyasu, Atul K. Bhan, Ellis L. Reinherz,

T-cell and B-cell Immunology

Research Article1 November 1996free access Cross-linking of T-cell receptors on double-positive thymocytes induces a cytokine-mediated stromal activation process linked to cell death. A. Lerner A. Lerner Laboratory of Immunobiology, Dana-Farber Cancer Institute, Boston, MA 02115, USA. Search for more papers by this author L. K. Clayton L. K. Clayton Laboratory of Immunobiology, Dana-Farber Cancer Institute, Boston, MA 02115, USA. Search for more papers by this author E. Mizoguchi E. Mizoguchi Laboratory of Immunobiology, Dana-Farber Cancer Institute, Boston, MA 02115, USA. Search for more papers by this author Y. Ghendler Y. Ghendler Laboratory of Immunobiology, Dana-Farber Cancer Institute, Boston, MA 02115, USA. Search for more papers by this author W. van Ewijk W. van Ewijk Laboratory of Immunobiology, Dana-Farber Cancer Institute, Boston, MA 02115, USA. Search for more papers by this author S. Koyasu S. Koyasu Laboratory of Immunobiology, Dana-Farber Cancer Institute, Boston, MA 02115, USA. Search for more papers by this author A. K. Bhan A. K. Bhan Laboratory of Immunobiology, Dana-Farber Cancer Institute, Boston, MA 02115, USA. Search for more papers by this author E. L. Reinherz E. L. Reinherz Laboratory of Immunobiology, Dana-Farber Cancer Institute, Boston, MA 02115, USA. Search for more papers by this author A. Lerner A. Lerner Laboratory of Immunobiology, Dana-Farber Cancer Institute, Boston, MA 02115, USA. Search for more papers by this author L. K. Clayton L. K. Clayton Laboratory of Immunobiology, Dana-Farber Cancer Institute, Boston, MA 02115, USA. Search for more papers by this author E. Mizoguchi E. Mizoguchi Laboratory of Immunobiology, Dana-Farber Cancer Institute, Boston, MA 02115, USA. Search for more papers by this author Y. Ghendler Y. Ghendler Laboratory of Immunobiology, Dana-Farber Cancer Institute, Boston, MA 02115, USA. Search for more papers by this author W. van Ewijk W. van Ewijk Laboratory of Immunobiology, Dana-Farber Cancer Institute, Boston, MA 02115, USA. Search for more papers by this author S. Koyasu S. Koyasu Laboratory of Immunobiology, Dana-Farber Cancer Institute, Boston, MA 02115, USA. Search for more papers by this author A. K. Bhan A. K. Bhan Laboratory of Immunobiology, Dana-Farber Cancer Institute, Boston, MA 02115, USA. Search for more papers by this author E. L. Reinherz E. L. Reinherz Laboratory of Immunobiology, Dana-Farber Cancer Institute, Boston, MA 02115, USA. Search for more papers by this author Author Information A. Lerner1, L. K. Clayton1, E. Mizoguchi1, Y. Ghendler1, W. Ewijk1, S. Koyasu1, A. K. Bhan1 and E. L. Reinherz1 1Laboratory of Immunobiology, Dana-Farber Cancer Institute, Boston, MA 02115, USA. The EMBO Journal (1996)15:5876-5887https://doi.org/10.1002/j.1460-2075.1996.tb00974.x PDFDownload PDF of article text and main figures. ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinked InMendeleyWechatReddit Figures & Info To investigate molecular events associated with the intrathymic process of negative selection, we established an in vivo system using an anti-CD3 epsilon monoclonal antibody to induce synchronous apoptosis in the thymus of AND T-cell receptor (TCR) transgenic RAG-2−/− mice in a non-selecting haplotype. This model eliminates endogenous negative selection as well as gene activation in the mature thymocyte compartment, offering an ideal source of tester (anti-CD3 epsilon-treated) and driver (untreated) thymus RNA for representational difference analysis (RDA). Fourteen mRNA sequences that are up-regulated in the thymuses of such mice 2–6 h after anti-CD3 epsilon treatment were identified. Surprisingly, the majority of these transcripts were derived from stromal cells rather than the TCR-cross-linked CD4+CD8+TCRlow thymocytes including the macrophage products IL-1, the chemokine Mig and the transcription factor LRG-21. IFN-gamma secretion from the CD4+CD8+TCRlow thymocytes regulates macrophage Mig production. Three other cytokines (IL-4, GM-CSF and TNF-alpha), known to activate a variety of stromal cells, are also induced in the same thymocyte population undergoing apoptosis. Expression of a TNF-alpha-inducible gene, B94, in stromal cells after TCR ligation further supports the notion of cross-talk between thymocytes and stroma. Thus, TCR-triggered immature thymocytes elaborate cytokines which may regulate the delivery of further signals from stromal cells required for apoptosis. Previous ArticleNext Article Volume 15Issue 211 November 1996In this issue RelatedDetailsLoading ...