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 naive 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 naive CD8+ T cells, whereas the maintenance of memory CD8+ T cells is IRF4-independent.
雑誌名
European Journal of Immunology
巻
48
号
8
ページ
1319 - 1328
発行年
2018-08
出版者
WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim
ISSN
00142980
DOI
10.1002/eji.201747120
権利
c 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.
著者版フラグ
author
引用
European Journal of Immunology, 48(8), pp.1319-1328; 2018
Differential requirements for IRF4 in the clonal expansion and homeostatic proliferation of naive and memory murine CD8+ T?cells
EJI48_1319.pdf
(3.02MB)
NAOSITEについて