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Differential requirements for IRF4 in the clonal expansion and homeostatic proliferation of naive and memory murine CD8+ T cells


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タイトル: Differential requirements for IRF4 in the clonal expansion and homeostatic proliferation of naive and memory murine CD8+ T cells
著者: Miyakoda, Mana / Honma, Kiri / Kimura, Daisuke / Akbari, Masoud / Kimura, Kazumi / Matsuyama, Toshifumi / Yui, Katsuyuki
発行日: 2018年 8月
出版者: WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim
引用: European Journal of Immunology, 48(8), pp.1319-1328; 2018
抄録: Interferon regulatory factor 4 (IRF4) has critical roles in immune cell differentiation and function and is indispensable for clonal expansion and effector function in T cells. Here, we demonstrate that the AKT pathway is impaired in murine CD8+ T cells lacking IRF4. The expression of phosphatase and tensin homolog (PTEN), a negative regulator of the AKT pathway, was elevated in Irf4−/− CD8+ T cells. Inhibition of PTEN partially rescued downstream events, suggesting that PTEN constitutes a checkpoint in the IRF4-mediated regulation of cell signaling. Despite the clonal expansion defect, in the absence of IRF4, memory-like CD8+ T cells could be generated and maintained, although unable to expand in recall responses. The homeostatic proliferation of naïve Irf4−/− CD8+ T cells was impaired, whereas their number eventually reached a level similar to that of wild-type CD8+ T cells. Conversely, memory-like Irf4−/− CD8+ T cells underwent homeostatic proliferation in a manner similar to that of wild-type memory CD8+ T cells. These results suggest that IRF4 regulates the clonal expansion of CD8+ T cells at least in part via the AKT signaling pathway. Moreover, IRF4 regulates the homeostatic proliferation of naïve CD8+ T cells, whereas the maintenance of memory CD8+ T cells is IRF4-independent.
キーワード: CD8+Tcells / Homeostasis / Memory cell / Signal transduction / Transcription factors
URI: http://hdl.handle.net/10069/38570
ISSN: 00142980
DOI: 10.1002/eji.201747120
権利: © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim. This is the peer reviewed version of the following article:European Journal of Immunology, 48(8), pp.1319-1328; 2018 , which has been published in final form at 10.1002/eji.201747120. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Use of Self-Archived Versions.
資料タイプ: Journal Article
原稿種類: author
出現コレクション:110 学術雑誌論文

引用URI : http://hdl.handle.net/10069/38570

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