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| Content Provider | World Health Organization (WHO)-Global Index Medicus |
|---|---|
| Author | Magiera, Lukasz Hoffmann, Anja De La Roche, Maike Fearon, Douglas T. Thaventhiran, James E. D. Lingel, Holger Brunner-weinzierl, Monika |
| Description | Author Affiliation: Thaventhiran JE ( Department of Immunology, Division of Infection and Immunity, University College London, Royal Free Hospital, London NW3 2QG, United Kingdom.); |
| 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. |
| ISSN | 00278424 |
| e-ISSN | 10916490 |
| Journal | Proceedings of the National Academy of Sciences of the United States of America |
| Issue Number | 33 |
| Volume Number | 109 |
| Language | English |
| Publisher | National Academy of Sciences |
| Publisher Date | 2012-08-01 |
| Publisher Place | United States |
| Access Restriction | Open |
| Subject Keyword | CD8-Positive T-Lymphocytes Enzymology Immunology CTLA-4 Antigen Metabolism Lymphocyte Activation Protein-Serine-Threonine Kinases Signal Transduction Transcription Factors Animals Antigens, CD80 Antigens, CD86 Cytology Cell Differentiation Cell Membrane Enzyme Activation Ligands Mice Research Support, Non-U.S. Gov't Multidisciplinary |
| Content Type | Text |
| Resource Type | Article |
| Subject | Multidisciplinary |
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