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ResearchIn-Press PreviewAIDS/HIVImmunology Open Access | 10.1172/jci.insight.136648

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

Rachel L. Rutishauser,1 Christian Deo T. Deguit,1 Joseph Hiatt,3 Franziska Blaeschke,3 Theodore L. Roth,3 Lynn Wang,1 Kyle A. Raymond,4 Carly E. Starke,5 Joseph C. Mudd,5 Wenxuan Chen,1 Carolyn P. Smullin,1 Rodrigo Matus-Nicodemos,6 Rebecca Hoh,1 Melissa R. Krone,7 Frederick M. Hecht,8 Christopher D. Pilcher,1 Jeffrey N. Martin,7 Richard A. Koup,9 Daniel C. Douek,6 Jason M. Brenchley,5 Rafick-Pierre Sékaly,10 Satish K. Pillai,4 Alexander Marson,1 Steven G. Deeks,1 Joseph M. McCune,1 and Peter W. Hunt1

1Department of Medicine, University of California, San Francisco, San Franciscoo, United States of America

2Department of Medicine, University of California, San Francisco, San Francisco, United States of America

3Department of Microbiology and Immunology, University of California, San Francisco, San Francisco, United States of America

4Department of Laboratory Medicine, University of California, San Francisco, San Francisco, United States of America

5Barrier Immunity Section, Laboratory of Viral Diseases, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, United States of America

6Human Immunology Section, Vaccine Research Center, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, United States of America

7Department of Epidemiology and Biostatistics, University of California, San Francisco, San Francisco, United States of America

8Department of Medicine, University of California, San Franciso, San Francisco, United States of America

9Immunology Laboratory, Vaccine Research Center, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, United States of America

10Department of Pathology, Case Western Reserve University, Cleveland, United States of America

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1Department of Medicine, University of California, San Francisco, San Franciscoo, United States of America

2Department of Medicine, University of California, San Francisco, San Francisco, United States of America

3Department of Microbiology and Immunology, University of California, San Francisco, San Francisco, United States of America

4Department of Laboratory Medicine, University of California, San Francisco, San Francisco, United States of America

5Barrier Immunity Section, Laboratory of Viral Diseases, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, United States of America

6Human Immunology Section, Vaccine Research Center, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, United States of America

7Department of Epidemiology and Biostatistics, University of California, San Francisco, San Francisco, United States of America

8Department of Medicine, University of California, San Franciso, San Francisco, United States of America

9Immunology Laboratory, Vaccine Research Center, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, United States of America

10Department of Pathology, Case Western Reserve University, Cleveland, United States of America

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1Department of Medicine, University of California, San Francisco, San Franciscoo, United States of America

2Department of Medicine, University of California, San Francisco, San Francisco, United States of America

3Department of Microbiology and Immunology, University of California, San Francisco, San Francisco, United States of America

4Department of Laboratory Medicine, University of California, San Francisco, San Francisco, United States of America

5Barrier Immunity Section, Laboratory of Viral Diseases, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, United States of America

6Human Immunology Section, Vaccine Research Center, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, United States of America

7Department of Epidemiology and Biostatistics, University of California, San Francisco, San Francisco, United States of America

8Department of Medicine, University of California, San Franciso, San Francisco, United States of America

9Immunology Laboratory, Vaccine Research Center, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, United States of America

10Department of Pathology, Case Western Reserve University, Cleveland, United States of America

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1Department of Medicine, University of California, San Francisco, San Franciscoo, United States of America

2Department of Medicine, University of California, San Francisco, San Francisco, United States of America

3Department of Microbiology and Immunology, University of California, San Francisco, San Francisco, United States of America

4Department of Laboratory Medicine, University of California, San Francisco, San Francisco, United States of America

5Barrier Immunity Section, Laboratory of Viral Diseases, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, United States of America

6Human Immunology Section, Vaccine Research Center, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, United States of America

7Department of Epidemiology and Biostatistics, University of California, San Francisco, San Francisco, United States of America

8Department of Medicine, University of California, San Franciso, San Francisco, United States of America

9Immunology Laboratory, Vaccine Research Center, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, United States of America

10Department of Pathology, Case Western Reserve University, Cleveland, United States of America

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1Department of Medicine, University of California, San Francisco, San Franciscoo, United States of America

2Department of Medicine, University of California, San Francisco, San Francisco, United States of America

3Department of Microbiology and Immunology, University of California, San Francisco, San Francisco, United States of America

4Department of Laboratory Medicine, University of California, San Francisco, San Francisco, United States of America

5Barrier Immunity Section, Laboratory of Viral Diseases, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, United States of America

6Human Immunology Section, Vaccine Research Center, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, United States of America

7Department of Epidemiology and Biostatistics, University of California, San Francisco, San Francisco, United States of America

8Department of Medicine, University of California, San Franciso, San Francisco, United States of America

9Immunology Laboratory, Vaccine Research Center, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, United States of America

10Department of Pathology, Case Western Reserve University, Cleveland, United States of America

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1Department of Medicine, University of California, San Francisco, San Franciscoo, United States of America

2Department of Medicine, University of California, San Francisco, San Francisco, United States of America

3Department of Microbiology and Immunology, University of California, San Francisco, San Francisco, United States of America

4Department of Laboratory Medicine, University of California, San Francisco, San Francisco, United States of America

5Barrier Immunity Section, Laboratory of Viral Diseases, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, United States of America

6Human Immunology Section, Vaccine Research Center, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, United States of America

7Department of Epidemiology and Biostatistics, University of California, San Francisco, San Francisco, United States of America

8Department of Medicine, University of California, San Franciso, San Francisco, United States of America

9Immunology Laboratory, Vaccine Research Center, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, United States of America

10Department of Pathology, Case Western Reserve University, Cleveland, United States of America

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1Department of Medicine, University of California, San Francisco, San Franciscoo, United States of America

2Department of Medicine, University of California, San Francisco, San Francisco, United States of America

3Department of Microbiology and Immunology, University of California, San Francisco, San Francisco, United States of America

4Department of Laboratory Medicine, University of California, San Francisco, San Francisco, United States of America

5Barrier Immunity Section, Laboratory of Viral Diseases, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, United States of America

6Human Immunology Section, Vaccine Research Center, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, United States of America

7Department of Epidemiology and Biostatistics, University of California, San Francisco, San Francisco, United States of America

8Department of Medicine, University of California, San Franciso, San Francisco, United States of America

9Immunology Laboratory, Vaccine Research Center, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, United States of America

10Department of Pathology, Case Western Reserve University, Cleveland, United States of America

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2Department of Medicine, University of California, San Francisco, San Francisco, United States of America

3Department of Microbiology and Immunology, University of California, San Francisco, San Francisco, United States of America

4Department of Laboratory Medicine, University of California, San Francisco, San Francisco, United States of America

5Barrier Immunity Section, Laboratory of Viral Diseases, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, United States of America

6Human Immunology Section, Vaccine Research Center, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, United States of America

7Department of Epidemiology and Biostatistics, University of California, San Francisco, San Francisco, United States of America

8Department of Medicine, University of California, San Franciso, San Francisco, United States of America

9Immunology Laboratory, Vaccine Research Center, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, United States of America

10Department of Pathology, Case Western Reserve University, Cleveland, United States of America

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2Department of Medicine, University of California, San Francisco, San Francisco, United States of America

3Department of Microbiology and Immunology, University of California, San Francisco, San Francisco, United States of America

4Department of Laboratory Medicine, University of California, San Francisco, San Francisco, United States of America

5Barrier Immunity Section, Laboratory of Viral Diseases, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, United States of America

6Human Immunology Section, Vaccine Research Center, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, United States of America

7Department of Epidemiology and Biostatistics, University of California, San Francisco, San Francisco, United States of America

8Department of Medicine, University of California, San Franciso, San Francisco, United States of America

9Immunology Laboratory, Vaccine Research Center, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, United States of America

10Department of Pathology, Case Western Reserve University, Cleveland, United States of America

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1Department of Medicine, University of California, San Francisco, San Franciscoo, United States of America

2Department of Medicine, University of California, San Francisco, San Francisco, United States of America

3Department of Microbiology and Immunology, University of California, San Francisco, San Francisco, United States of America

4Department of Laboratory Medicine, University of California, San Francisco, San Francisco, United States of America

5Barrier Immunity Section, Laboratory of Viral Diseases, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, United States of America

6Human Immunology Section, Vaccine Research Center, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, United States of America

7Department of Epidemiology and Biostatistics, University of California, San Francisco, San Francisco, United States of America

8Department of Medicine, University of California, San Franciso, San Francisco, United States of America

9Immunology Laboratory, Vaccine Research Center, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, United States of America

10Department of Pathology, Case Western Reserve University, Cleveland, United States of America

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2Department of Medicine, University of California, San Francisco, San Francisco, United States of America

3Department of Microbiology and Immunology, University of California, San Francisco, San Francisco, United States of America

4Department of Laboratory Medicine, University of California, San Francisco, San Francisco, United States of America

5Barrier Immunity Section, Laboratory of Viral Diseases, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, United States of America

6Human Immunology Section, Vaccine Research Center, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, United States of America

7Department of Epidemiology and Biostatistics, University of California, San Francisco, San Francisco, United States of America

8Department of Medicine, University of California, San Franciso, San Francisco, United States of America

9Immunology Laboratory, Vaccine Research Center, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, United States of America

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2Department of Medicine, University of California, San Francisco, San Francisco, United States of America

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4Department of Laboratory Medicine, University of California, San Francisco, San Francisco, United States of America

5Barrier Immunity Section, Laboratory of Viral Diseases, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, United States of America

6Human Immunology Section, Vaccine Research Center, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, United States of America

7Department of Epidemiology and Biostatistics, University of California, San Francisco, San Francisco, United States of America

8Department of Medicine, University of California, San Franciso, San Francisco, United States of America

9Immunology Laboratory, Vaccine Research Center, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, United States of America

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2Department of Medicine, University of California, San Francisco, San Francisco, United States of America

3Department of Microbiology and Immunology, University of California, San Francisco, San Francisco, United States of America

4Department of Laboratory Medicine, University of California, San Francisco, San Francisco, United States of America

5Barrier Immunity Section, Laboratory of Viral Diseases, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, United States of America

6Human Immunology Section, Vaccine Research Center, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, United States of America

7Department of Epidemiology and Biostatistics, University of California, San Francisco, San Francisco, United States of America

8Department of Medicine, University of California, San Franciso, San Francisco, United States of America

9Immunology Laboratory, Vaccine Research Center, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, United States of America

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4Department of Laboratory Medicine, University of California, San Francisco, San Francisco, United States of America

5Barrier Immunity Section, Laboratory of Viral Diseases, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, United States of America

6Human Immunology Section, Vaccine Research Center, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, United States of America

7Department of Epidemiology and Biostatistics, University of California, San Francisco, San Francisco, United States of America

8Department of Medicine, University of California, San Franciso, San Francisco, United States of America

9Immunology Laboratory, Vaccine Research Center, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, United States of America

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2Department of Medicine, University of California, San Francisco, San Francisco, United States of America

3Department of Microbiology and Immunology, University of California, San Francisco, San Francisco, United States of America

4Department of Laboratory Medicine, University of California, San Francisco, San Francisco, United States of America

5Barrier Immunity Section, Laboratory of Viral Diseases, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, United States of America

6Human Immunology Section, Vaccine Research Center, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, United States of America

7Department of Epidemiology and Biostatistics, University of California, San Francisco, San Francisco, United States of America

8Department of Medicine, University of California, San Franciso, San Francisco, United States of America

9Immunology Laboratory, Vaccine Research Center, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, United States of America

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2Department of Medicine, University of California, San Francisco, San Francisco, United States of America

3Department of Microbiology and Immunology, University of California, San Francisco, San Francisco, United States of America

4Department of Laboratory Medicine, University of California, San Francisco, San Francisco, United States of America

5Barrier Immunity Section, Laboratory of Viral Diseases, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, United States of America

6Human Immunology Section, Vaccine Research Center, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, United States of America

7Department of Epidemiology and Biostatistics, University of California, San Francisco, San Francisco, United States of America

8Department of Medicine, University of California, San Franciso, San Francisco, United States of America

9Immunology Laboratory, Vaccine Research Center, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, United States of America

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4Department of Laboratory Medicine, University of California, San Francisco, San Francisco, United States of America

5Barrier Immunity Section, Laboratory of Viral Diseases, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, United States of America

6Human Immunology Section, Vaccine Research Center, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, United States of America

7Department of Epidemiology and Biostatistics, University of California, San Francisco, San Francisco, United States of America

8Department of Medicine, University of California, San Franciso, San Francisco, United States of America

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3Department of Microbiology and Immunology, University of California, San Francisco, San Francisco, United States of America

4Department of Laboratory Medicine, University of California, San Francisco, San Francisco, United States of America

5Barrier Immunity Section, Laboratory of Viral Diseases, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, United States of America

6Human Immunology Section, Vaccine Research Center, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, United States of America

7Department of Epidemiology and Biostatistics, University of California, San Francisco, San Francisco, United States of America

8Department of Medicine, University of California, San Franciso, San Francisco, United States of America

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1Department of Medicine, University of California, San Francisco, San Franciscoo, United States of America

2Department of Medicine, University of California, San Francisco, San Francisco, United States of America

3Department of Microbiology and Immunology, University of California, San Francisco, San Francisco, United States of America

4Department of Laboratory Medicine, University of California, San Francisco, San Francisco, United States of America

5Barrier Immunity Section, Laboratory of Viral Diseases, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, United States of America

6Human Immunology Section, Vaccine Research Center, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, United States of America

7Department of Epidemiology and Biostatistics, University of California, San Francisco, San Francisco, United States of America

8Department of Medicine, University of California, San Franciso, San Francisco, United States of America

9Immunology Laboratory, Vaccine Research Center, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, United States of America

10Department of Pathology, Case Western Reserve University, Cleveland, United States of America

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1Department of Medicine, University of California, San Francisco, San Franciscoo, United States of America

2Department of Medicine, University of California, San Francisco, San Francisco, United States of America

3Department of Microbiology and Immunology, University of California, San Francisco, San Francisco, United States of America

4Department of Laboratory Medicine, University of California, San Francisco, San Francisco, United States of America

5Barrier Immunity Section, Laboratory of Viral Diseases, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, United States of America

6Human Immunology Section, Vaccine Research Center, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, United States of America

7Department of Epidemiology and Biostatistics, University of California, San Francisco, San Francisco, United States of America

8Department of Medicine, University of California, San Franciso, San Francisco, United States of America

9Immunology Laboratory, Vaccine Research Center, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, United States of America

10Department of Pathology, Case Western Reserve University, Cleveland, United States of America

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1Department of Medicine, University of California, San Francisco, San Franciscoo, United States of America

2Department of Medicine, University of California, San Francisco, San Francisco, United States of America

3Department of Microbiology and Immunology, University of California, San Francisco, San Francisco, United States of America

4Department of Laboratory Medicine, University of California, San Francisco, San Francisco, United States of America

5Barrier Immunity Section, Laboratory of Viral Diseases, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, United States of America

6Human Immunology Section, Vaccine Research Center, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, United States of America

7Department of Epidemiology and Biostatistics, University of California, San Francisco, San Francisco, United States of America

8Department of Medicine, University of California, San Franciso, San Francisco, United States of America

9Immunology Laboratory, Vaccine Research Center, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, United States of America

10Department of Pathology, Case Western Reserve University, Cleveland, United States of America

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1Department of Medicine, University of California, San Francisco, San Franciscoo, United States of America

2Department of Medicine, University of California, San Francisco, San Francisco, United States of America

3Department of Microbiology and Immunology, University of California, San Francisco, San Francisco, United States of America

4Department of Laboratory Medicine, University of California, San Francisco, San Francisco, United States of America

5Barrier Immunity Section, Laboratory of Viral Diseases, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, United States of America

6Human Immunology Section, Vaccine Research Center, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, United States of America

7Department of Epidemiology and Biostatistics, University of California, San Francisco, San Francisco, United States of America

8Department of Medicine, University of California, San Franciso, San Francisco, United States of America

9Immunology Laboratory, Vaccine Research Center, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, United States of America

10Department of Pathology, Case Western Reserve University, Cleveland, United States of America

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1Department of Medicine, University of California, San Francisco, San Franciscoo, United States of America

2Department of Medicine, University of California, San Francisco, San Francisco, United States of America

3Department of Microbiology and Immunology, University of California, San Francisco, San Francisco, United States of America

4Department of Laboratory Medicine, University of California, San Francisco, San Francisco, United States of America

5Barrier Immunity Section, Laboratory of Viral Diseases, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, United States of America

6Human Immunology Section, Vaccine Research Center, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, United States of America

7Department of Epidemiology and Biostatistics, University of California, San Francisco, San Francisco, United States of America

8Department of Medicine, University of California, San Franciso, San Francisco, United States of America

9Immunology Laboratory, Vaccine Research Center, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, United States of America

10Department of Pathology, Case Western Reserve University, Cleveland, United States of America

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1Department of Medicine, University of California, San Francisco, San Franciscoo, United States of America

2Department of Medicine, University of California, San Francisco, San Francisco, United States of America

3Department of Microbiology and Immunology, University of California, San Francisco, San Francisco, United States of America

4Department of Laboratory Medicine, University of California, San Francisco, San Francisco, United States of America

5Barrier Immunity Section, Laboratory of Viral Diseases, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, United States of America

6Human Immunology Section, Vaccine Research Center, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, United States of America

7Department of Epidemiology and Biostatistics, University of California, San Francisco, San Francisco, United States of America

8Department of Medicine, University of California, San Franciso, San Francisco, United States of America

9Immunology Laboratory, Vaccine Research Center, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, United States of America

10Department of Pathology, Case Western Reserve University, Cleveland, United States of America

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1Department of Medicine, University of California, San Francisco, San Franciscoo, United States of America

2Department of Medicine, University of California, San Francisco, San Francisco, United States of America

3Department of Microbiology and Immunology, University of California, San Francisco, San Francisco, United States of America

4Department of Laboratory Medicine, University of California, San Francisco, San Francisco, United States of America

5Barrier Immunity Section, Laboratory of Viral Diseases, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, United States of America

6Human Immunology Section, Vaccine Research Center, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, United States of America

7Department of Epidemiology and Biostatistics, University of California, San Francisco, San Francisco, United States of America

8Department of Medicine, University of California, San Franciso, San Francisco, United States of America

9Immunology Laboratory, Vaccine Research Center, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, United States of America

10Department of Pathology, Case Western Reserve University, Cleveland, United States of America

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1Department of Medicine, University of California, San Francisco, San Franciscoo, United States of America

2Department of Medicine, University of California, San Francisco, San Francisco, United States of America

3Department of Microbiology and Immunology, University of California, San Francisco, San Francisco, United States of America

4Department of Laboratory Medicine, University of California, San Francisco, San Francisco, United States of America

5Barrier Immunity Section, Laboratory of Viral Diseases, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, United States of America

6Human Immunology Section, Vaccine Research Center, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, United States of America

7Department of Epidemiology and Biostatistics, University of California, San Francisco, San Francisco, United States of America

8Department of Medicine, University of California, San Franciso, San Francisco, United States of America

9Immunology Laboratory, Vaccine Research Center, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, United States of America

10Department of Pathology, Case Western Reserve University, Cleveland, United States of America

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Published December 22, 2020 - More info

JCI Insight. https://doi.org/10.1172/jci.insight.136648.
Copyright © 2020, Rutishauser et al. 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/.
Published December 22, 2020 - Version history
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Abstract

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 non-human primates naturally controlling HIV/SIV infection express more of the transcription factor, TCF-1, than non-controllers. 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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  • Version 1 (December 22, 2020): In-Press Preview

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