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TCF-1 regulates HIV-specific CD8(+) T cell expansion capacity

Although many HIV cure strategies seek to expand HIV-specific CD8(+) T cells to control the virus, all are likely to fail if cellular exhaustion is not prevented. A loss in stem-like memory properties (i.e., the ability to proliferate and generate secondary effector cells) is a key feature of exhaus...

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Autores principales: Rutishauser, Rachel L., Deguit, Christian Deo T., Hiatt, Joseph, Blaeschke, Franziska, Roth, Theodore L., Wang, Lynn, Raymond, Kyle A., Starke, Carly E., Mudd, Joseph C., Chen, Wenxuan, Smullin, Carolyn, Matus-Nicodemos, Rodrigo, Hoh, Rebecca, Krone, Melissa, Hecht, Frederick M., Pilcher, Christopher D., Martin, Jeffrey N., Koup, Richard A., Douek, Daniel C., Brenchley, Jason M., Sékaly, Rafick-Pierre, Pillai, Satish K., Marson, Alexander, Deeks, Steven G., McCune, Joseph M., Hunt, Peter W.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: American Society for Clinical Investigation 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7934879/
https://www.ncbi.nlm.nih.gov/pubmed/33351785
http://dx.doi.org/10.1172/jci.insight.136648
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author Rutishauser, Rachel L.
Deguit, Christian Deo T.
Hiatt, Joseph
Blaeschke, Franziska
Roth, Theodore L.
Wang, Lynn
Raymond, Kyle A.
Starke, Carly E.
Mudd, Joseph C.
Chen, Wenxuan
Smullin, Carolyn
Matus-Nicodemos, Rodrigo
Hoh, Rebecca
Krone, Melissa
Hecht, Frederick M.
Pilcher, Christopher D.
Martin, Jeffrey N.
Koup, Richard A.
Douek, Daniel C.
Brenchley, Jason M.
Sékaly, Rafick-Pierre
Pillai, Satish K.
Marson, Alexander
Deeks, Steven G.
McCune, Joseph M.
Hunt, Peter W.
author_facet Rutishauser, Rachel L.
Deguit, Christian Deo T.
Hiatt, Joseph
Blaeschke, Franziska
Roth, Theodore L.
Wang, Lynn
Raymond, Kyle A.
Starke, Carly E.
Mudd, Joseph C.
Chen, Wenxuan
Smullin, Carolyn
Matus-Nicodemos, Rodrigo
Hoh, Rebecca
Krone, Melissa
Hecht, Frederick M.
Pilcher, Christopher D.
Martin, Jeffrey N.
Koup, Richard A.
Douek, Daniel C.
Brenchley, Jason M.
Sékaly, Rafick-Pierre
Pillai, Satish K.
Marson, Alexander
Deeks, Steven G.
McCune, Joseph M.
Hunt, Peter W.
author_sort Rutishauser, Rachel L.
collection PubMed
description Although many HIV cure strategies seek to expand HIV-specific CD8(+) T cells to control the virus, all are likely to fail if cellular exhaustion is not prevented. A loss in stem-like memory properties (i.e., the ability to proliferate and generate secondary effector cells) is a key feature of exhaustion; little is known, however, about how these properties are regulated in human virus–specific CD8(+) T cells. We found that virus-specific CD8(+) T cells from humans and nonhuman primates naturally controlling HIV/SIV infection express more of the transcription factor TCF-1 than noncontrollers. HIV-specific CD8(+) T cell TCF-1 expression correlated with memory marker expression and expansion capacity and declined with antigenic stimulation. CRISPR-Cas9 editing of TCF-1 in human primary T cells demonstrated a direct role in regulating expansion capacity. Collectively, these data suggest that TCF-1 contributes to the regulation of the stem-like memory property of secondary expansion capacity of HIV-specific CD8(+) T cells, and they provide a rationale for exploring the enhancement of this pathway in T cell–based therapeutic strategies for HIV.
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spelling pubmed-79348792021-03-09 TCF-1 regulates HIV-specific CD8(+) T cell expansion capacity Rutishauser, Rachel L. Deguit, Christian Deo T. Hiatt, Joseph Blaeschke, Franziska Roth, Theodore L. Wang, Lynn Raymond, Kyle A. Starke, Carly E. Mudd, Joseph C. Chen, Wenxuan Smullin, Carolyn Matus-Nicodemos, Rodrigo Hoh, Rebecca Krone, Melissa Hecht, Frederick M. Pilcher, Christopher D. Martin, Jeffrey N. Koup, Richard A. Douek, Daniel C. Brenchley, Jason M. Sékaly, Rafick-Pierre Pillai, Satish K. Marson, Alexander Deeks, Steven G. McCune, Joseph M. Hunt, Peter W. JCI Insight Research Article Although many HIV cure strategies seek to expand HIV-specific CD8(+) T cells to control the virus, all are likely to fail if cellular exhaustion is not prevented. A loss in stem-like memory properties (i.e., the ability to proliferate and generate secondary effector cells) is a key feature of exhaustion; little is known, however, about how these properties are regulated in human virus–specific CD8(+) T cells. We found that virus-specific CD8(+) T cells from humans and nonhuman primates naturally controlling HIV/SIV infection express more of the transcription factor TCF-1 than noncontrollers. HIV-specific CD8(+) T cell TCF-1 expression correlated with memory marker expression and expansion capacity and declined with antigenic stimulation. CRISPR-Cas9 editing of TCF-1 in human primary T cells demonstrated a direct role in regulating expansion capacity. Collectively, these data suggest that TCF-1 contributes to the regulation of the stem-like memory property of secondary expansion capacity of HIV-specific CD8(+) T cells, and they provide a rationale for exploring the enhancement of this pathway in T cell–based therapeutic strategies for HIV. American Society for Clinical Investigation 2021-02-08 /pmc/articles/PMC7934879/ /pubmed/33351785 http://dx.doi.org/10.1172/jci.insight.136648 Text en © 2021 Rutishauser et al. http://creativecommons.org/licenses/by/4.0/ This work is licensed under the Creative Commons Attribution 4.0 International License. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Research Article
Rutishauser, Rachel L.
Deguit, Christian Deo T.
Hiatt, Joseph
Blaeschke, Franziska
Roth, Theodore L.
Wang, Lynn
Raymond, Kyle A.
Starke, Carly E.
Mudd, Joseph C.
Chen, Wenxuan
Smullin, Carolyn
Matus-Nicodemos, Rodrigo
Hoh, Rebecca
Krone, Melissa
Hecht, Frederick M.
Pilcher, Christopher D.
Martin, Jeffrey N.
Koup, Richard A.
Douek, Daniel C.
Brenchley, Jason M.
Sékaly, Rafick-Pierre
Pillai, Satish K.
Marson, Alexander
Deeks, Steven G.
McCune, Joseph M.
Hunt, Peter W.
TCF-1 regulates HIV-specific CD8(+) T cell expansion capacity
title TCF-1 regulates HIV-specific CD8(+) T cell expansion capacity
title_full TCF-1 regulates HIV-specific CD8(+) T cell expansion capacity
title_fullStr TCF-1 regulates HIV-specific CD8(+) T cell expansion capacity
title_full_unstemmed TCF-1 regulates HIV-specific CD8(+) T cell expansion capacity
title_short TCF-1 regulates HIV-specific CD8(+) T cell expansion capacity
title_sort tcf-1 regulates hiv-specific cd8(+) t cell expansion capacity
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7934879/
https://www.ncbi.nlm.nih.gov/pubmed/33351785
http://dx.doi.org/10.1172/jci.insight.136648
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