Persistent Antigen and Prolonged AKT-mTORC1 Activation Underlie Memory CD8 T Cell Impairment in the Absence of CD4 T Cells
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Chen_Persistent antigen.pdf
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Author(s)
Li, Yingzhong
Shen, Chase
Zhu, Bingdong
Chen, Jianzhu
Shi, Feng
Eisen, Herman N.
Date Issued
August 2015
Journal
Journal of Immunology
Publisher
American Association of Immunologists
Citation
Li, Yingzhong et al. “Persistent Antigen and Prolonged AKT–mTORC1 Activation Underlie Memory CD8 T Cell Impairment in the Absence of CD4 T Cells.” The Journal of Immunology 195.4 (2015): 1591–1598.
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Author's final manuscript
Abstract
Recall responses by memory CD8 T cells are impaired in the absence of CD4 T cells. Although several mechanisms have been proposed, the molecular basis is still largely unknown. Using a local influenza virus infection in the respiratory tract and the lung of CD4[superscript −/−] mice, we show that memory CD8 T cell impairment is limited to the lungs and the lung-draining lymph nodes, where viral Ags are unusually persistent and abundant in these mice. Persistent Ag exposure results in prolonged activation of the AKT–mTORC1 pathway in Ag-specific CD8 T cells, favoring their development into effector memory T cells at the expense of central memory T cells, and inhibition of mTORC1 by rapamycin largely corrects the impairment by promoting central memory T cell development. The findings suggest that the prolonged AKT–mTORC1 activation driven by persistent Ag is a critical mechanism underlying the impaired memory CD8 T cell development and responses in the absence of CD4 T cells.
MIT Department
Massachusetts Institute of Technology. Department of Biology
Koch Institute for Integrative Cancer Research at MIT
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DOI of Published Version
https://doi.org/10.4049/jimmunol.1500451
