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Restricted Expression of the Thymoproteasome Is Required for Thymic Selection and Peripheral Homeostasis of CD8+ T Cells

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Title: Restricted Expression of the Thymoproteasome Is Required for Thymic Selection and Peripheral Homeostasis of CD8+ T Cells
Authors: Tomaru, Utano Browse this author →KAKEN DB
Konno, Saori Browse this author
Miyajima, Syota Browse this author
Kimoto, Rikuto Browse this author
Onodera, Mari Browse this author
Kiuchi, Shizuka Browse this author
Murata, Shigeo Browse this author
Ishizu, Akihiro Browse this author →KAKEN DB
Kasahara, Masanori Browse this author →KAKEN DB
Keywords: thymoproteasome
thymic epithelial cells
thymic selection
naïve T cells
memory T cells
self peptide
autoimmune disease
Issue Date: 15-Jan-2019
Publisher: Cell Press
Journal Title: Cell Reports
Volume: 26
Issue: 3
Start Page: 639
End Page: 651
Publisher DOI: 10.1016/j.celrep.2018.12.078
Abstract: The thymoproteasome subunit β5t is specifically expressed in cortical thymic epithelial cells (TECs) and generates unique peptides to support positive selection. In this study, using a mouse model ubiquitously expressing β5t, we showed that aberrant expression of self-peptides generated by β5t affects CD8+ T cell homeostasis, including thymic selection and maintenance of the peripheral naive pool of CD8+ T cells. In mice in which β5t was expressed both in cortical and medullary TECs, the abundance of CD8+ lineage thymocytes was reduced, and extra-thymic expression of β5t caused accumulation of CD8+ T cells with the memory or exhausted phenotype and induced autoreactive T cell responses. We found that thymoproteasomes are essential for positive selection but that the subsequent change in peptide repertoire in the medulla is also crucial for thymic selection and that β5t-derived peptide must be confined to the thymus to avoid autoimmunity in peripheral tissues.
Type: article
Appears in Collections:医学院・医学研究院 (Graduate School of Medicine / Faculty of Medicine) > 雑誌発表論文等 (Peer-reviewed Journal Articles, etc)

Submitter: 外丸 詩野

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