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A functional subset of CD8+ T cells during chronic exhaustion is defined by SIRPα expression

Author

Listed:
  • Lara M. Myers

    (Rocky Mountain Laboratories)

  • Michal Caspi Tal

    (Stanford University School of Medicine)

  • Laughing Bear Torrez Dulgeroff

    (Stanford University School of Medicine)

  • Aaron B. Carmody

    (Rocky Mountain Laboratories, NIAID, NIH)

  • Ronald J. Messer

    (Rocky Mountain Laboratories)

  • Gunsagar Gulati

    (Stanford University School of Medicine)

  • Ying Ying Yiu

    (Stanford University School of Medicine)

  • Matthew M. Staron

    (Rocky Mountain Laboratories, NIAID, NIH
    AbbVie Bioresearch Center)

  • Cesar Lopez Angel

    (Stanford University School of Medicine)

  • Rahul Sinha

    (Stanford University School of Medicine)

  • Maxim Markovic

    (Stanford University School of Medicine)

  • Edward A. Pham

    (Stanford University School of Medicine
    Stanford University School of Medicine)

  • Benjamin Fram

    (Stanford University School of Medicine)

  • Aijaz Ahmed

    (Stanford University School of Medicine)

  • Aaron M. Newman

    (Stanford University School of Medicine
    Stanford University School of Medicine)

  • Jeffrey S. Glenn

    (Stanford University School of Medicine
    Stanford University School of Medicine)

  • Mark M. Davis

    (Stanford University School of Medicine)

  • Susan M. Kaech

    (Yale School of Medicine
    Salk Institute)

  • Irving L. Weissman

    (Stanford University School of Medicine)

  • Kim J. Hasenkrug

    (Rocky Mountain Laboratories)

Abstract

Prolonged exposure of CD8+ T cells to antigenic stimulation, as in chronic viral infections, leads to a state of diminished function termed exhaustion. We now demonstrate that even during exhaustion there is a subset of functional CD8+ T cells defined by surface expression of SIRPα, a protein not previously reported on lymphocytes. On SIRPα+ CD8+ T cells, expression of co-inhibitory receptors is counterbalanced by expression of co-stimulatory receptors and it is only SIRPα+ cells that actively proliferate, transcribe IFNγ and show cytolytic activity. Furthermore, target cells that express the ligand for SIRPα, CD47, are more susceptible to CD8+ T cell-killing in vivo. SIRPα+ CD8+ T cells are evident in mice infected with Friend retrovirus, LCMV Clone 13, and in patients with chronic HCV infections. Furthermore, therapeutic blockade of PD-L1 to reinvigorate CD8+ T cells during chronic infection expands the cytotoxic subset of SIRPα+ CD8+ T cells.

Suggested Citation

  • Lara M. Myers & Michal Caspi Tal & Laughing Bear Torrez Dulgeroff & Aaron B. Carmody & Ronald J. Messer & Gunsagar Gulati & Ying Ying Yiu & Matthew M. Staron & Cesar Lopez Angel & Rahul Sinha & Maxim , 2019. "A functional subset of CD8+ T cells during chronic exhaustion is defined by SIRPα expression," Nature Communications, Nature, vol. 10(1), pages 1-15, December.
    • Handle: RePEc:nat:natcom:v:10:y:2019:i:1:d:10.1038_s41467-019-08637-9
    DOI: 10.1038/s41467-019-08637-9
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