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The full spectrum of human naive T cells

Nature Reviews Immunologyvolume 18pages363373 (2018) | Download Citation


Naive T cells have long been regarded as a developmentally synchronized and fairly homogeneous and quiescent cell population, the size of which depends on age, thymic output and prior infections. However, there is increasing evidence that naive T cells are heterogeneous in phenotype, function, dynamics and differentiation status. Current strategies to identify naive T cells should be adjusted to take this heterogeneity into account. Here, we provide an integrated, revised view of the naive T cell compartment and discuss its implications for healthy ageing, neonatal immunity and T cell reconstitution following haematopoietic stem cell transplantation.

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The authors apologize to those colleagues whose relevant work was not included in this Review owing to space constraints. The authors thank R. de Boer, M. Hazenberg and L. Meyaard for critically reading the manuscript and for helpful comments and A. Boltjes for support with the figures.

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Nature Reviews Immunology thanks R. Kedl and the other anonymous reviewer(s), for their contribution to the peer review of this work.

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  1. Laboratory of Translational Immunology, University Medical Centre Utrecht, Utrecht, Netherlands

    • Theo van den Broek
    • , José A. M. Borghans
    •  & Femke van Wijk
  2. Department of Medical Microbiology, University Medical Centre Utrecht, Utrecht, Netherlands

    • Theo van den Broek
  3. Program in Cellular and Molecular Medicine, Boston Children’s Hospital and Department of Pediatrics, Harvard Medical School, Boston, MA, USA

    • Theo van den Broek


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T.v.d.B., J.A.M.B. and F.v.W. wrote the manuscript and contributed to reviewing the literature and the review and editing of this article.

Competing interests

The authors declare no competing interests.

Corresponding author

Correspondence to Femke van Wijk.



The condition of having an abnormally low level of lymphocytes in the circulation.

Haematopoietic stem cell transplantation

(HSCT). Treatment of recipients with irradiation and/or chemotherapy followed by the infusion of cells containing haematopoietic stem and progenitor cells with or without immune cells derived from individuals of the same species.

Homeostatic proliferation

This term can refer to two different phenomena: the steady-state maintenance of T cells through self-renewal (minimal division) and the process by which T cells in lymphopenic conditions rapidly proliferate to reconstitute the T cell pool, also called lymphopenia-induced proliferation.

Virtual memory T cells

Antigen-inexperienced memory-phenotype T cells, which may be induced by T cell receptor cross reactivity, low-affinity peptide and/or MHC ligands and certain cytokines.

Mature naive T cells

Naive T cells that have matured in secondary lymphoid organs following thymic egress and are no longer recent thymic emigrants.

T cell receptor excision circles

(TRECs). Small, stable circles of DNA excised during T cell receptor gene rearrangement in the thymus.

Simpson’s diversity index

A measure of diversity that takes into account the number of clones present, as well as the relative abundance of each clone.

Repertoire skewedness

The extent to which a repertoire deviates from a situation where all clones occur equally frequently.

Thymic output

The amount of T cells that successfully exit the thymus into the periphery after intrathymic selection.

Graft-versus-host disease

(GVHD). An inflammatory complication following the transplantation of stem cells or organs to a genetically different person caused by donor immune cells that recognize the recipient’s cells and tissues as foreign.

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