Elite control of HIV is associated with distinct functional and transcriptional signatures in lymphoid tissue CD8+ T cells

Son Nguyen; Claire Deleage; Samuel Darko; Amy Ransier; Duc P. Truong; Divyansh Agarwal; Alberto Sada Japp; Vincent H. Wu; Leticia Kuri-Cervantes; Mohamed Abdel-Mohsen; Perla M. Del Rio Estrada; Yuria Ablanedo-Terrazas; Emma Gostick; James A. Hoxie; Nancy R. Zhang; Ali Naji; Gustavo Reyes-Terán; Jacob D. Estes; David A. Price; Daniel C. Douek; Steven G. Deeks; Marcus Buggert; Michael R. Betts

doi:10.1126/scitranslmed.aax4077

Research ArticleHIV

Elite control of HIV is associated with distinct functional and transcriptional signatures in lymphoid tissue CD8⁺ T cells

View ORCID ProfileSon Nguyen¹,
View ORCID ProfileClaire Deleage²,
View ORCID ProfileSamuel Darko³,
Amy Ransier³,
View ORCID ProfileDuc P. Truong⁴,
View ORCID ProfileDivyansh Agarwal⁵,
View ORCID ProfileAlberto Sada Japp¹,
View ORCID ProfileVincent H. Wu¹,
View ORCID ProfileLeticia Kuri-Cervantes¹,
View ORCID ProfileMohamed Abdel-Mohsen ⁶,
View ORCID ProfilePerla M. Del Rio Estrada⁷,
Yuria Ablanedo-Terrazas⁷,
View ORCID ProfileEmma Gostick⁸,
View ORCID ProfileJames A. Hoxie⁹,
View ORCID ProfileNancy R. Zhang⁵,
View ORCID ProfileAli Naji¹⁰,
View ORCID ProfileGustavo Reyes-Terán⁷,
View ORCID ProfileJacob D. Estes ¹¹,¹²,
View ORCID ProfileDavid A. Price ⁸,
Daniel C. Douek ³,
View ORCID ProfileSteven G. Deeks ¹³,
View ORCID ProfileMarcus Buggert¹⁴,* and
View ORCID ProfileMichael R. Betts ¹,*,†

¹Department of Microbiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
²AIDS and Cancer Virus Program, Frederick National Laboratory for Cancer Research, Leidos Biomedical Research Inc., Frederick, MD 21702, USA.
³Human Immunology Section, Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
⁴Department of Mathematics, Southern Methodist University, Dallas, TX 75205, USA.
⁵Department of Statistics, University of Pennsylvania, Philadelphia, PA 19104, USA.
⁶The Wistar Institute, Philadelphia, PA 19104, USA.
⁷Departamento de Investigación en Enfermedades Infecciosas, Instituto Nacional de Enfermedades Respiratorias, Mexico City 14080, Mexico.
⁸Division of Infection and Immunity, Cardiff University School of Medicine, Cardiff CF14 4XN, UK.
⁹Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
¹⁰Department of Surgery, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
¹¹Vaccine and Gene Therapy Institute, Oregon Health and Science University, Portland, OR 97239, USA.
¹²Division of Pathobiology and Immunology, Oregon National Primate Research Center, Oregon Health and Science University, Portland, OR 97239, USA.
¹³Department of Medicine, University of California, San Francisco General Hospital, San Francisco, CA 94110, USA.
¹⁴Department of Medicine Huddinge, Karolinska Institutet, Karolinska University Hospital Huddinge, 14186 Stockholm, Sweden.

↵†Corresponding author. Email: betts{at}pennmedicine.upenn.edu

↵* These authors contributed equally to this work.

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Science Translational Medicine 18 Dec 2019:
Vol. 11, Issue 523, eaax4077
DOI: 10.1126/scitranslmed.aax4077

Son Nguyen

1Department of Microbiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.

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Claire Deleage

2AIDS and Cancer Virus Program, Frederick National Laboratory for Cancer Research, Leidos Biomedical Research Inc., Frederick, MD 21702, USA.

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Samuel Darko

3Human Immunology Section, Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.

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Amy Ransier

3Human Immunology Section, Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.

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Duc P. Truong

4Department of Mathematics, Southern Methodist University, Dallas, TX 75205, USA.

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Divyansh Agarwal

5Department of Statistics, University of Pennsylvania, Philadelphia, PA 19104, USA.

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Alberto Sada Japp

1Department of Microbiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.

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Vincent H. Wu

1Department of Microbiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.

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Leticia Kuri-Cervantes

1Department of Microbiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.

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Mohamed Abdel-Mohsen

6The Wistar Institute, Philadelphia, PA 19104, USA.

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Perla M. Del Rio Estrada

7Departamento de Investigación en Enfermedades Infecciosas, Instituto Nacional de Enfermedades Respiratorias, Mexico City 14080, Mexico.

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Yuria Ablanedo-Terrazas

7Departamento de Investigación en Enfermedades Infecciosas, Instituto Nacional de Enfermedades Respiratorias, Mexico City 14080, Mexico.

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Emma Gostick

8Division of Infection and Immunity, Cardiff University School of Medicine, Cardiff CF14 4XN, UK.

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James A. Hoxie

9Department of Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.

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Nancy R. Zhang

5Department of Statistics, University of Pennsylvania, Philadelphia, PA 19104, USA.

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Ali Naji

10Department of Surgery, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.

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Gustavo Reyes-Terán

7Departamento de Investigación en Enfermedades Infecciosas, Instituto Nacional de Enfermedades Respiratorias, Mexico City 14080, Mexico.

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Jacob D. Estes

11Vaccine and Gene Therapy Institute, Oregon Health and Science University, Portland, OR 97239, USA.

12Division of Pathobiology and Immunology, Oregon National Primate Research Center, Oregon Health and Science University, Portland, OR 97239, USA.

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David A. Price

8Division of Infection and Immunity, Cardiff University School of Medicine, Cardiff CF14 4XN, UK.

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Daniel C. Douek

3Human Immunology Section, Vaccine Research Center, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.

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Steven G. Deeks

13Department of Medicine, University of California, San Francisco General Hospital, San Francisco, CA 94110, USA.

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Marcus Buggert

14Department of Medicine Huddinge, Karolinska Institutet, Karolinska University Hospital Huddinge, 14186 Stockholm, Sweden.

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Michael R. Betts

1Department of Microbiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.

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For correspondence: betts@pennmedicine.upenn.edu

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