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CD8+ T Cell Biology in Cytokine Storm Syndromes

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Cytokine Storm Syndrome

Abstract

Familial forms of hemophagocytic lymphohistiocytosis (HLH) are caused by loss-of-function mutations in genes encoding perforin as well as those required for release of perforin-containing cytotoxic granule constituent. Perforin is expressed by subsets of CD8+ T cells and NK cells, representing lymphocytes that share mechanism of target cell killing yet display distinct modes of target cell recognition. Here, we highlight recent findings concerning the genetics of familial HLH that implicate CD8+ T cells in the pathogenesis of HLH and discuss mechanistic insights from animal models as well as patients that reveal how CD8+ T cells may contribute to or drive disease, at least in part through release of IFN-γ. Intriguingly, CD8+ T cells and NK cells may act differentially in severe hyperinflammatory diseases such as HLH. We also discuss how CD8+ T cells may promote or drive pathology in other cytokine release syndromes (CSS). Moreover, we review the molecular mechanisms underpinning CD8+ T cell-mediated lymphocyte cytotoxicity, key to the development of familial HLH. Together, recent insights to the pathophysiology of CSS in general and HLH in particular are providing promising new therapeutic targets.

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Acknowledgments

The authors would like to thank members of the Bryceson laboratory as well as colleagues in the HLH research field for insightful discussions.

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Authors and Affiliations

  1. Department of Medicine, Center for Hematology and Regenerative Medicine, Karolinska Institutet, Stockholm, Sweden

    Takuya Sekine, Donatella Galgano, Giovanna P. Casoni & Yenan T. Bryceson

  2. Childhood Cancer Research Unit, Department of Women’s and Children’s Health, Karolinska Institutet, Karolinska University Hospital Solna, Stockholm, Sweden

    Marie Meeths

  3. Clinical Genetics Unit, Department of Molecular Medicine and Surgery, and Center for Molecular Medicine, Karolinska Institutet, Karolinska University Hospital, Solna, Stockholm, Sweden

    Marie Meeths

  4. Department of Clinical Sciences, Broegelmann Research Laboratory, University of Bergen, Bergen, Norway

    Yenan T. Bryceson

  5. Department of Medicine, Center for Hematology and Regenerative Medicine, Karolinska Institutet, Huddinge, Sweden

    Yenan T. Bryceson

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  1. Takuya Sekine
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  2. Donatella Galgano
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  5. Yenan T. Bryceson
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Correspondence to Yenan T. Bryceson .

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  1. UAB School of Medicine, University of Alabama at Birmingham, Birmingham, AL, USA

    Randy Q. Cron

  2. Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA

    Edward M. Behrens

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Sekine, T., Galgano, D., Casoni, G.P., Meeths, M., Bryceson, Y.T. (2019). CD8+ T Cell Biology in Cytokine Storm Syndromes. In: Cron, R., Behrens, E. (eds) Cytokine Storm Syndrome. Springer, Cham. https://doi.org/10.1007/978-3-030-22094-5_9

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