Inhibitory signaling sustains a distinct early memory CD8+ T cell precursor that is resistant to DNA damage

Jonathan B. Johnnidis; Yuki Muroyama; Shin Foong Ngiow; Zeyu Chen; Sasikanth Manne; Zhangying Cai; Shufei Song; Jesse M. Platt; Jason M. Schenkel; Mohamed Abdel-Hakeem; Jean-Christophe Beltra; Allison R. Greenplate; Mohammed-Alkhatim A. Ali; Kito Nzingha; Josephine R. Giles; Christelle Harly; John Attanasio; Kristen E. Pauken; Bertram Bengsch; Michael A. Paley; Vesselin T. Tomov; Makoto Kurachi; Dario A. A. Vignali; Arlene H. Sharpe; Steven L. Reiner; Avinash Bhandoola; F. Bradley Johnson; E. John Wherry

doi:10.1126/sciimmunol.abe3702

Research ArticleT CELLS

Inhibitory signaling sustains a distinct early memory CD8⁺ T cell precursor that is resistant to DNA damage

View ORCID ProfileJonathan B. Johnnidis ¹,²,³,*,
View ORCID ProfileYuki Muroyama ²,³,*,
View ORCID ProfileShin Foong Ngiow ²,³,⁴,
Zeyu Chen²,³,
View ORCID ProfileSasikanth Manne²,³,
Zhangying Cai⁵,
View ORCID ProfileShufei Song⁶,
Jesse M. Platt ⁷,⁸,
View ORCID ProfileJason M. Schenkel⁹,¹⁰,
View ORCID ProfileMohamed Abdel-Hakeem ²,³,
View ORCID ProfileJean-Christophe Beltra ²,³,⁴,
View ORCID ProfileAllison R. Greenplate²,³,
Mohammed-Alkhatim A. Ali²,³,
View ORCID ProfileKito Nzingha²,³,
View ORCID ProfileJosephine R. Giles ²,³,⁴,
View ORCID ProfileChristelle Harly¹¹,¹²,¹³,
View ORCID ProfileJohn Attanasio³,
View ORCID ProfileKristen E. Pauken¹⁴,¹⁵,
View ORCID ProfileBertram Bengsch ¹⁶,¹⁷,
View ORCID ProfileMichael A. Paley ¹⁸,
Vesselin T. Tomov³,¹⁹,
View ORCID ProfileMakoto Kurachi²⁰,
View ORCID ProfileDario A. A. Vignali ²¹,²²,²³,
View ORCID ProfileArlene H. Sharpe ¹⁴,¹⁵,
View ORCID ProfileSteven L. Reiner²⁴,
View ORCID ProfileAvinash Bhandoola¹¹,
View ORCID ProfileF. Bradley Johnson ⁶ and
View ORCID ProfileE. John Wherry ²,³,⁴,†

¹Department of Biology, University of Pennsylvania, Philadelphia, PA 19104, USA.
²Department of Systems Pharmacology and Translational Therapeutics, University of Pennsylvania, Philadelphia, PA 19104, USA.
³Institute for Immunology, University of Pennsylvania, Philadelphia, PA 19104, USA.
⁴Parker Institute for Cancer Immunotherapy, University of Pennsylvania, Philadelphia, PA 19104, USA.
⁵Division of Biology and Biomedical Sciences, Washington University, St. Louis, MO 63110, USA.
⁶Department of Pathology and Laboratory Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
⁷Division of Gastroenterology, Department of Medicine, Massachusetts General Hospital, Boston, MA 02114, USA.
⁸Whitehead Institute for Biomedical Research, Cambridge, MA 02142, USA.
⁹Department of Pathology, Brigham and Women’s Hospital, Boston, MA 02115, USA.
¹⁰David H. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
¹¹T-Cell Biology and Development Unit, Laboratory of Genome Integrity, Center for Cancer Research, National Cancer Institute, Bethesda, MD 20892, USA.
¹²Université de Nantes, INSERM, CNRS, CRCINA, Nantes, France.
¹³LabEx IGO ‘Immunotherapy, Graft, Oncology’, Nantes, France.
¹⁴Department of Immunology, Blavatnik Institute, Harvard Medical School, Boston, MA 02115, USA.
¹⁵Evergrande Center for Immunologic Diseases, Harvard Medical School and Brigham and Women’s Hospital, Boston, MA 02115, USA.
¹⁶Department of Medicine II, Gastroenterology, Hepatology, Endocrinology, and Infectious Diseases, University Medical Center Freiburg, Germany.
¹⁷Signaling Research Centers BIOSS and CIBSS, University of Freiburg, Freiburg, Germany.
¹⁸Department of Medicine, Washington University in Saint Louis School of Medicine, St. Louis, MO 63110, USA.
¹⁹Department of Medicine, Division of Gastroenterology, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA 19104, USA.
²⁰Department of Molecular Genetics, Graduate School of Medicine, Kanazawa University, Kanazawa, Japan.
²¹Department of Immunology, University of Pittsburgh School of Medicine, Pittsburgh, PA 15213, USA.
²²Tumor Microenvironment Center, UPMC Hillman Cancer Center, Pittsburgh PA 15232, USA.
²³Cancer Immunology and Immunotherapy Program, UPMC Hillman Cancer Center, Pittsburgh, PA 15232, USA.
²⁴Department of Microbiology and Immunology and Department of Pediatrics, Columbia University, New York, NY 10032, USA.

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

↵* These authors contributed equally to this work.

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Science Immunology 15 Jan 2021:
Vol. 6, Issue 55, eabe3702
DOI: 10.1126/sciimmunol.abe3702

Jonathan B. Johnnidis

1Department of Biology, University of Pennsylvania, Philadelphia, PA 19104, USA.

2Department of Systems Pharmacology and Translational Therapeutics, University of Pennsylvania, Philadelphia, PA 19104, USA.

3Institute for Immunology, University of Pennsylvania, Philadelphia, PA 19104, USA.

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Yuki Muroyama

2Department of Systems Pharmacology and Translational Therapeutics, University of Pennsylvania, Philadelphia, PA 19104, USA.

3Institute for Immunology, University of Pennsylvania, Philadelphia, PA 19104, USA.

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Shin Foong Ngiow

2Department of Systems Pharmacology and Translational Therapeutics, University of Pennsylvania, Philadelphia, PA 19104, USA.

3Institute for Immunology, University of Pennsylvania, Philadelphia, PA 19104, USA.

4Parker Institute for Cancer Immunotherapy, University of Pennsylvania, Philadelphia, PA 19104, USA.

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Zeyu Chen

2Department of Systems Pharmacology and Translational Therapeutics, University of Pennsylvania, Philadelphia, PA 19104, USA.

3Institute for Immunology, University of Pennsylvania, Philadelphia, PA 19104, USA.

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Sasikanth Manne

2Department of Systems Pharmacology and Translational Therapeutics, University of Pennsylvania, Philadelphia, PA 19104, USA.

3Institute for Immunology, University of Pennsylvania, Philadelphia, PA 19104, USA.

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Zhangying Cai

5Division of Biology and Biomedical Sciences, Washington University, St. Louis, MO 63110, USA.

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Shufei Song

6Department of Pathology and Laboratory Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.

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Jesse M. Platt

7Division of Gastroenterology, Department of Medicine, Massachusetts General Hospital, Boston, MA 02114, USA.

8Whitehead Institute for Biomedical Research, Cambridge, MA 02142, USA.

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Jason M. Schenkel

9Department of Pathology, Brigham and Women’s Hospital, Boston, MA 02115, USA.

10David H. Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.

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Mohamed Abdel-Hakeem

2Department of Systems Pharmacology and Translational Therapeutics, University of Pennsylvania, Philadelphia, PA 19104, USA.

3Institute for Immunology, University of Pennsylvania, Philadelphia, PA 19104, USA.

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Jean-Christophe Beltra

2Department of Systems Pharmacology and Translational Therapeutics, University of Pennsylvania, Philadelphia, PA 19104, USA.

3Institute for Immunology, University of Pennsylvania, Philadelphia, PA 19104, USA.

4Parker Institute for Cancer Immunotherapy, University of Pennsylvania, Philadelphia, PA 19104, USA.

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Allison R. Greenplate

2Department of Systems Pharmacology and Translational Therapeutics, University of Pennsylvania, Philadelphia, PA 19104, USA.

3Institute for Immunology, University of Pennsylvania, Philadelphia, PA 19104, USA.

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Mohammed-Alkhatim A. Ali

2Department of Systems Pharmacology and Translational Therapeutics, University of Pennsylvania, Philadelphia, PA 19104, USA.

3Institute for Immunology, University of Pennsylvania, Philadelphia, PA 19104, USA.

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Kito Nzingha

2Department of Systems Pharmacology and Translational Therapeutics, University of Pennsylvania, Philadelphia, PA 19104, USA.

3Institute for Immunology, University of Pennsylvania, Philadelphia, PA 19104, USA.

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Josephine R. Giles

2Department of Systems Pharmacology and Translational Therapeutics, University of Pennsylvania, Philadelphia, PA 19104, USA.

3Institute for Immunology, University of Pennsylvania, Philadelphia, PA 19104, USA.

4Parker Institute for Cancer Immunotherapy, University of Pennsylvania, Philadelphia, PA 19104, USA.

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Christelle Harly

11T-Cell Biology and Development Unit, Laboratory of Genome Integrity, Center for Cancer Research, National Cancer Institute, Bethesda, MD 20892, USA.

12Université de Nantes, INSERM, CNRS, CRCINA, Nantes, France.

13LabEx IGO ‘Immunotherapy, Graft, Oncology’, Nantes, France.

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John Attanasio

3Institute for Immunology, University of Pennsylvania, Philadelphia, PA 19104, USA.

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Kristen E. Pauken

14Department of Immunology, Blavatnik Institute, Harvard Medical School, Boston, MA 02115, USA.

15Evergrande Center for Immunologic Diseases, Harvard Medical School and Brigham and Women’s Hospital, Boston, MA 02115, USA.

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Bertram Bengsch

16Department of Medicine II, Gastroenterology, Hepatology, Endocrinology, and Infectious Diseases, University Medical Center Freiburg, Germany.

17Signaling Research Centers BIOSS and CIBSS, University of Freiburg, Freiburg, Germany.

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Michael A. Paley

18Department of Medicine, Washington University in Saint Louis School of Medicine, St. Louis, MO 63110, USA.

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Vesselin T. Tomov

3Institute for Immunology, University of Pennsylvania, Philadelphia, PA 19104, USA.

19Department of Medicine, Division of Gastroenterology, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA 19104, USA.

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Makoto Kurachi

20Department of Molecular Genetics, Graduate School of Medicine, Kanazawa University, Kanazawa, Japan.

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Dario A. A. Vignali

21Department of Immunology, University of Pittsburgh School of Medicine, Pittsburgh, PA 15213, USA.

22Tumor Microenvironment Center, UPMC Hillman Cancer Center, Pittsburgh PA 15232, USA.

23Cancer Immunology and Immunotherapy Program, UPMC Hillman Cancer Center, Pittsburgh, PA 15232, USA.

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Arlene H. Sharpe

14Department of Immunology, Blavatnik Institute, Harvard Medical School, Boston, MA 02115, USA.

15Evergrande Center for Immunologic Diseases, Harvard Medical School and Brigham and Women’s Hospital, Boston, MA 02115, USA.

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Steven L. Reiner

24Department of Microbiology and Immunology and Department of Pediatrics, Columbia University, New York, NY 10032, USA.

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Avinash Bhandoola

11T-Cell Biology and Development Unit, Laboratory of Genome Integrity, Center for Cancer Research, National Cancer Institute, Bethesda, MD 20892, USA.

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F. Bradley Johnson

6Department of Pathology and Laboratory Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.

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E. John Wherry

2Department of Systems Pharmacology and Translational Therapeutics, University of Pennsylvania, Philadelphia, PA 19104, USA.

3Institute for Immunology, University of Pennsylvania, Philadelphia, PA 19104, USA.

4Parker Institute for Cancer Immunotherapy, University of Pennsylvania, Philadelphia, PA 19104, USA.

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For correspondence: wherry@pennmedicine.upenn.edu

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Inhibitory signaling sustains a distinct early memory CD8⁺ T cell precursor that is resistant to DNA damage

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