Persistent Antigen and Prolonged AKT-mTORC1 Activation Underlie Memory CD8 T Cell Impairment in the Absence of CD4 T Cells
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 me...
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| Format: | Article |
| Language: | en_US |
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American Association of Immunologists
2017
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| Online Access: | http://hdl.handle.net/1721.1/107900 https://orcid.org/0000-0002-4213-2496 https://orcid.org/0000-0002-5687-6154 https://orcid.org/0000-0003-3938-9634 |
| _version_ | 1826202105563578368 |
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| author | Li, Yingzhong Shen, Chase Zhu, Bingdong Chen, Jianzhu Shi, Feng Eisen, Herman N. |
| author2 | Massachusetts Institute of Technology. Department of Biology |
| author_facet | Massachusetts Institute of Technology. Department of Biology Li, Yingzhong Shen, Chase Zhu, Bingdong Chen, Jianzhu Shi, Feng Eisen, Herman N. |
| author_sort | Li, Yingzhong |
| collection | MIT |
| description | 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. |
| first_indexed | 2024-09-23T12:02:16Z |
| format | Article |
| id | mit-1721.1/107900 |
| institution | Massachusetts Institute of Technology |
| language | en_US |
| last_indexed | 2024-09-23T12:02:16Z |
| publishDate | 2017 |
| publisher | American Association of Immunologists |
| record_format | dspace |
| spelling | mit-1721.1/1079002022-10-01T07:45:36Z Persistent Antigen and Prolonged AKT-mTORC1 Activation Underlie Memory CD8 T Cell Impairment in the Absence of CD4 T Cells Li, Yingzhong Shen, Chase Zhu, Bingdong Chen, Jianzhu Shi, Feng Eisen, Herman N. Massachusetts Institute of Technology. Department of Biology Koch Institute for Integrative Cancer Research at MIT Li, Yingzhong Shen, Chase Zhu, Bingdong Eisen, Herman N Chen, Jianzhu Shi, Feng 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. National Institutes of Health (U.S.) (Grant AI69208) Singapore. National Research Foundation (Singapore-MIT Alliance for Research and Technology (SMART). Infectious Disease Research Program) Ivan R. Cottrell Professorship and Research Fund National Cancer Institute (U.S.) (David H. Koch Institute for Integrative Cancer Research at MIT. Support (Core) Grant P30-CA14051) 2017-04-06T15:43:11Z 2017-04-06T15:43:11Z 2015-08 2015-02 Article http://purl.org/eprint/type/JournalArticle 0022-1767 1550-6606 http://hdl.handle.net/1721.1/107900 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. https://orcid.org/0000-0002-4213-2496 https://orcid.org/0000-0002-5687-6154 https://orcid.org/0000-0003-3938-9634 en_US http://dx.doi.org/10.4049/jimmunol.1500451 Journal of Immunology Creative Commons Attribution-Noncommercial-Share Alike http://creativecommons.org/licenses/by-nc-sa/4.0/ application/pdf American Association of Immunologists PMC |
| spellingShingle | Li, Yingzhong Shen, Chase Zhu, Bingdong Chen, Jianzhu Shi, Feng Eisen, Herman N. Persistent Antigen and Prolonged AKT-mTORC1 Activation Underlie Memory CD8 T Cell Impairment in the Absence of CD4 T Cells |
| title | Persistent Antigen and Prolonged AKT-mTORC1 Activation Underlie Memory CD8 T Cell Impairment in the Absence of CD4 T Cells |
| title_full | Persistent Antigen and Prolonged AKT-mTORC1 Activation Underlie Memory CD8 T Cell Impairment in the Absence of CD4 T Cells |
| title_fullStr | Persistent Antigen and Prolonged AKT-mTORC1 Activation Underlie Memory CD8 T Cell Impairment in the Absence of CD4 T Cells |
| title_full_unstemmed | Persistent Antigen and Prolonged AKT-mTORC1 Activation Underlie Memory CD8 T Cell Impairment in the Absence of CD4 T Cells |
| title_short | Persistent Antigen and Prolonged AKT-mTORC1 Activation Underlie Memory CD8 T Cell Impairment in the Absence of CD4 T Cells |
| title_sort | persistent antigen and prolonged akt mtorc1 activation underlie memory cd8 t cell impairment in the absence of cd4 t cells |
| url | http://hdl.handle.net/1721.1/107900 https://orcid.org/0000-0002-4213-2496 https://orcid.org/0000-0002-5687-6154 https://orcid.org/0000-0003-3938-9634 |
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