After virus exposure, early bystander naïve CD8 T cell activation relies on NAD+ salvage metabolism

Namit Holay; Barry E Kennedy; J Patrick Murphy; Prathyusha Konda; Michael Giacomantonio; Tatjana Brauer-Chapin; Joao A Paulo; Vishnupriyan Kumar; Youra Kim; Mariam Elaghil; Gary Sisson; Derek Clements; Christopher Richardson; Steven P Gygi; Shashi Gujar

doi:10.3389/fimmu.2022.1047661

After virus exposure, early bystander naïve CD8 T cell activation relies on NAD⁺ salvage metabolism

Front Immunol. 2023 Feb 1:13:1047661. doi: 10.3389/fimmu.2022.1047661. eCollection 2022.

Authors

Namit Holay¹, Barry E Kennedy^{1

2}, J Patrick Murphy^{1

3}, Prathyusha Konda^{4

5}, Michael Giacomantonio¹, Tatjana Brauer-Chapin^{1

6}, Joao A Paulo⁶, Vishnupriyan Kumar¹, Youra Kim¹, Mariam Elaghil^{1

2}, Gary Sisson³, Derek Clements^{1

7}, Christopher Richardson^{4

8

9}, Steven P Gygi⁶, Shashi Gujar^{1

4

10

11

12}

Affiliations

¹ Department of Pathology, Dalhousie University, Halifax, NS, Canada.
² IMV Inc, Halifax, NS, Canada.
³ Department of Biology, University of Prince Edward Island, Charlottetown, PEI, Canada.
⁴ Department of Microbiology and Immunology, Dalhousie University, Halifax, NS, Canada.
⁵ Dana Farber Cancer Institute, Harvard Medical School, Boston, MA, United States.
⁶ Department of Cell Biology, Harvard Medical School, Harvard University, Boston, MA, United States.
⁷ Department of Microbiology and Immunology, Stanford University, Stanford, CA, United States.
⁸ Canadian Centre for Vaccinology, IWK Health Centre, Goldbloom Pavilion, Halifax, NS, Canada.
⁹ Department of Pediatrics, Dalhousie University, Halifax, NS, Canada.
¹⁰ Department of Biology, Dalhousie University, Halifax, NS, Canada.
¹¹ Beatrice Hunter Cancer Research Institute, Halifax, NS, Canada.
¹² Cancer Immunotherapy: Innovation & Global Partnerships, Faculty of Medicine, Dalhousie University, Halifax, NS, Canada.

Abstract

CD8 T cells play a central role in antiviral immunity. Type I interferons are among the earliest responders after virus exposure and can cause extensive reprogramming and antigen-independent bystander activation of CD8 T cells. Although bystander activation of pre-existing memory CD8 T cells is known to play an important role in host defense and immunopathology, its impact on naïve CD8 T cells remains underappreciated. Here we report that exposure to reovirus, both in vitro or in vivo, promotes bystander activation of naïve CD8 T cells within 24 hours and that this distinct subtype of CD8 T cell displays an innate, antiviral, type I interferon sensitized signature. The induction of bystander naïve CD8 T cells is STAT1 dependent and regulated through nicotinamide phosphoribosyl transferase (NAMPT)-mediated enzymatic actions within NAD⁺ salvage metabolic biosynthesis. These findings identify a novel aspect of CD8 T cell activation following virus infection with implications for human health and physiology.

Keywords: CD8 T cells; NAD+ salvage metabolism; antiviral immunity; bystander activation; immunometabolism; metabolic reprogramming; naïve CD8 T cells; type I interferons.

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

MeSH terms

Antigens
Antiviral Agents
CD8-Positive T-Lymphocytes
Humans
NAD*
Virus Diseases*

Substances

NAD
Antigens
Antiviral Agents

Abstract

Publication types

MeSH terms

Substances

Grants and funding