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Probing Human NK Cell Biology Using Human Immune System (HIS) Mice

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Natural Killer Cells

Part of the book series: Current Topics in Microbiology and Immunology ((CT MICROBIOLOGY,volume 395))

Abstract

Our incomplete understanding of the mechanisms that orchestrate human lymphocyte differentiation and condition human immune responses is in part due to the limited access to normal human tissue samples that can inform on these complex processes. In addition, in vitro culture conditions fail to recapitulate the three-dimensional microenvironments that influence cell–cell interactions and impact on immune outcomes. Small animals provide a preclinical model to dissect and probe immunity and over the past decades, development of immunodeficient hosts that can be engrafted with human hematopoietic precursors and mature cells have led to the development of new in vivo models to study human lymphocyte development and function. Natural killer (NK) cells are implicated in the recognition and elimination of pathogen-infected and transformed cells and belong to a family of diverse innate lymphoid cells (ILCs) that provide early immune defense against disease. Here, we summarize the use of humanized mouse models for the study of NK cell and group 1 ILCs and their respective roles in immunity and tissue homeostasis.

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Abbreviations

BRG:

BALB/c Rag2 −/− Il2rg −/−

DC:

Dendritic cell

Flt3L:

FMS-like tyrosine kinase 3 ligand

HIS:

Human immune system

HLA:

Human leukocyte antigen

HSC:

Hematopoietic stem cell

IFN:

Interferon

IL:

Interleukin

ILC:

Innate lymphoid cell

KIR:

Killer cell immunoglobulin-like receptor

GM-CSF:

Granulocyte–macrophage colony-stimulating factor

M-CSF:

Macrophage colony-stimulating factor

MHC:

Major histocompatibility complex

NK:

Natural killer

NOG, NSG:

NOD/SCID/Il2rg −/−

PRKDC:

Protein kinase, DNA-activated, catalytic polypeptide

SCF:

Stem cell factor

SIRPα:

Signal regulatory protein α

TPO:

Thrombopoietin

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Acknowledgements

Research in the Di Santo laboratory is supported by grants from the Institut Pasteur, Inserm, ANR, Ligue Contre le Cancer and the ANRS. YL is supported by grants from the ANR (RPIB through the Im_HIS project) and from the LABEX ‘REVIVE.’

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Authors and Affiliations

  1. Innate Immunity Unit, Institut Pasteur, 25 rue du Docteur Roux, Paris, 75724, France

    Yan Li & James P. Di Santo

  2. Inserm U668, Paris, France

    Yan Li & James P. Di Santo

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  1. Yan Li
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  2. James P. Di Santo
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Correspondence to James P. Di Santo .

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Editors and Affiliations

  1. Assistance Publique des Hôpitaux de Marseille, Marseille 05, France and Centre d'Immunologie de Marseille-Luminy, Aix Marseille Université - INSERM - CNRS, Marseille 09, France

    Eric Vivier

  2. INSERM U 668, Pasteur Institute, Paris, Paris, France

    James Di Santo

  3. University of Genoa, Genova, Italy

    Alessandro Moretta

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Li, Y., Di Santo, J.P. (2015). Probing Human NK Cell Biology Using Human Immune System (HIS) Mice. In: Vivier, E., Di Santo, J., Moretta, A. (eds) Natural Killer Cells. Current Topics in Microbiology and Immunology, vol 395. Springer, Cham. https://doi.org/10.1007/82_2015_488

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