Activation of the Hippo pathway by CTLA-4 regulates the expression of Blimp-1 in the CD8+ T cell

Thaventhiran, J. E., Hoffmann, A., Magiera, L., de la Roche, M., Lingel, H., Brunner-Weinzierl, M., Fearon, D. T. (August 2012) Activation of the Hippo pathway by CTLA-4 regulates the expression of Blimp-1 in the CD8+ T cell. Proc Natl Acad Sci U S A, 109 (33). E2223-9. ISSN 1091-6490 (Electronic)0027-8424 (Linking)

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URL: http://www.ncbi.nlm.nih.gov/pubmed/22745171
DOI: 10.1073/pnas.1209115109

Abstract

During the primary response, the commitment of the CD8(+) T cell to Blimp-1 expression and the terminal differentiation that Blimp-1 induces must be timed so as not to impair the process of clonal expansion. We determined whether the Hippo pathway, which links cell-cell contact to differentiation in other cell lineages, controls Blimp-1 expression. Activating the CD8(+) T cell with antigen and IL-2 causes expression of the core Hippo pathway components, including the pivotal transcriptional cofactor Yap. Contact between activated CD8(+) T cells induces Hippo pathway-mediated Yap degradation and Blimp-1 expression; a Hippo-resistant, stable form of Yap suppresses Blimp-1 expression. Cytotoxic T lymphocyte antigen 4 (CTLA-4) and CD80 comprise the receptor-ligand pair that mediates contact-dependent Hippo pathway activation. In vivo, CD8(+) T cells expressing Hippo resistant-Yap or lacking CTLA-4 have diminished expression of the senescence marker, KLRG1, during a viral infection. The CTLA-4/Hippo pathway/Blimp-1 system may couple terminal differentiation of CD8(+) T cell with the magnitude of clonal expansion.

Item Type: Paper
Uncontrolled Keywords: Animals Antigens, CD80/metabolism Antigens, CD86/metabolism CD8-Positive T-Lymphocytes/cytology/ enzymology/ immunology CTLA-4 Antigen/ metabolism Cell Differentiation/immunology Cell Membrane/metabolism Enzyme Activation Ligands Lymphocyte Activation/ immunology Mice Protein-Serine-Threonine Kinases/ metabolism Signal Transduction/ immunology Transcription Factors/ metabolism
Subjects: organs, tissues, organelles, cell types and functions > cell types and functions > cell types > T cells
organs, tissues, organelles, cell types and functions > cell types and functions > cell types > T cells
organs, tissues, organelles, cell types and functions > cell types and functions > cell types > T cells
CSHL Authors:
Communities: CSHL labs > Fearon lab
Depositing User: Matt Covey
Date: 14 August 2012
Date Deposited: 22 Jul 2015 21:12
Last Modified: 08 Nov 2017 20:42
PMCID: PMC3421161
Related URLs:
URI: http://repository.cshl.edu/id/eprint/31642

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