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

作者：Thaventhiran James E D; Hoffmann Anja; Magiera Lukasz; de la Roche Maike; Lingel Holger; Brunner Weinzierl Monika; Fearon Douglas T^*

来源：Proceedings of the National Academy of Sciences, 2012, 109(33): E2223-E2229.

DOI：10.1073/pnas.1209115109

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.

• 出版日期2012-8-14
• 单位河北医科大学