Recent advances in iNKT cell development

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Abstract

Recent studies suggest that murine invariant natural killer T (iNKT) cell development culminates in three terminally differentiated iNKT cell subsets denoted as NKT1, 2, and 17 cells. Although these studies corroborate the significance of the subset division model, less is known about the factors driving subset commitment in iNKT cell progenitors. In this review, we discuss the latest findings in iNKT cell development, focusing in particular on how T-cell receptor signal strength steers iNKT cell progenitors toward specific subsets and how early progenitor cells can be identified. In addition, we will discuss the essential factors for their sustenance and functionality. A picture is emerging wherein the majority of thymic iNKT cells are mature effector cells retained in the organ rather than developing precursors.

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Most cited references 63

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Positive and negative selection of T cells.

Timothy Starr, Stephen C. Jameson, Kristin A. Hogquist (2003)

A functional immune system requires the selection of T lymphocytes expressing receptors that are major histocompatibility complex restricted but tolerant to self-antigens. This selection occurs predominantly in the thymus, where lymphocyte precursors first assemble a surface receptor. In this review we summarize the current state of the field regarding the natural ligands and molecular factors required for positive and negative selection and discuss a model for how these disparate outcomes can be signaled via the same receptor. We also discuss emerging data on the selection of regulatory T cells. Such cells require a high-affinity interaction with self-antigens, yet differentiate into regulatory cells instead of being eliminated.

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The BTB-zinc finger transcriptional regulator PLZF controls the development of invariant natural killer T cell effector functions.

Damian Kovalovsky, Olisambu U Uche, Sonia Eladad … (2008)

Invariant natural killer T cells (iNKT cells) have an innate immunity-like rapidity of response and the ability to modulate the effector functions of other cells. We show here that iNKT cells specifically expressed the BTB-zinc finger transcriptional regulator PLZF. In the absence of PLZF, iNKT cells developed, but they lacked many features of innate T cells. PLZF-deficient iNKT cells accumulated in lymph nodes rather than in the liver, did not express NK markers and did not have the characteristic activated phenotype. PLZF-deficient iNKT cells failed to secrete large amounts of interleukin 4 and interferon-gamma after activation; however, some cells produced either interleukin 4 or interferon-gamma but not both. PLZF, therefore, is an iNKT cell-specific transcription factor that is necessary for full functionality.

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Raising the NKT cell family.

Dale Godfrey, Sanda Stankovic, Alan G. Baxter (2010)

Natural killer T cells (NKT cells) are CD1d-restricted, lipid antigen-reactive, immunoregulatory T lymphocytes that can promote cell-mediated immunity to tumors and infectious organisms, including bacteria and viruses, yet paradoxically they can also suppress the cell-mediated immunity associated with autoimmune disease and allograft rejection. Furthermore, in some diseases, such as atherosclerosis and allergy, NKT cell activity can be deleterious to the host. Although the precise means by which these cells carry out such contrasting functions is unclear, recent studies have highlighted the existence of many functionally distinct NKT cell subsets. Because their frequency and number vary widely between individuals, it is important to understand the mechanisms that regulate the development and maintenance of NKT cells and subsets thereof, which is the subject of this review.

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Author and article information

Contributors

Kristin Hogquist: Role: ConceptualizationRole: Funding AcquisitionRole: Writing – Review & Editing

ORCID: https://orcid.org/0000-0001-9963-5687

Hristo Georgiev: Role: ConceptualizationRole: Writing – Original Draft Preparation

ORCID: https://orcid.org/0000-0003-1369-960X

Journal

Journal ID (nlm-ta): F1000Res

Journal ID (iso-abbrev): F1000Res

Journal ID (pmc): F1000Research

Title: F1000Research

Publisher: F1000 Research Limited (London, UK )

ISSN (Electronic): 2046-1402

Publication date (Electronic): 20 February 2020

Publication date Collection: 2020

Volume: 9

Electronic Location Identifier: F1000 Faculty Rev-127

Affiliations

[1 ]Center for Immunology, University of Minnesota, Minneapolis, MN, 55455, USA

Author notes

[a ] hogqu001@ 123456umn.edu

[b ] hgeorgie@ 123456umn.edu

No competing interests were disclosed.

Author information

Kristin Hogquist https://orcid.org/0000-0001-9963-5687

Hristo Georgiev https://orcid.org/0000-0003-1369-960X

Article

DOI: 10.12688/f1000research.21378.1

PMC ID: 7043113

PubMed ID: 32148771

SO-VID: 3fe1bae2-93a0-456c-94a2-0debace66986

License:

This is an open access article distributed under the terms of the Creative Commons Attribution Licence, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

History

Date accepted : 13 February 2020

Funding

Funded by: Deutsche Forschungsgemeinschaft ( DFG) fellowship

Award ID: GE3062/1-1

Funded by: National Institutes of Health

Award ID: R01AI140547

This work was supported by Deutsche Forschungsgemeinschaft (DFG) fellowship GE 3062/1-1 (to HG) and by National Institutes of Health grant R01 AI140547 (to KAH).

The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

Recent advances in iNKT cell development

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Most cited references 63

Positive and negative selection of T cells.

The BTB-zinc finger transcriptional regulator PLZF controls the development of invariant natural killer T cell effector functions.

Raising the NKT cell family.

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