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Post-thymic maturation: young T cells assert their individuality

Nature Reviews Immunology volume 11, pages 544–549 (2011)Cite this article

Subjects

Key Points

  • Recent thymic emigrants (RTEs), the youngest peripheral T cells, undergo progressive phenotypic and functional maturation during their first few weeks in the peripheral lymphoid tissue. Here, RTEs and their more mature, although still naive, T cell counterparts occupy largely overlapping niches.

  • RTEs are a functionally distinct subset of the peripheral T cell pool, characterized by reduced cytokine and transcription factor expression compared with mature naive T cells.

  • Post-thymic maturation requires thymic egress and access to secondary lymphoid organs; however, the molecular trigger(s) that drive RTE maturation are still unknown, although the transcriptional repressor NKAP may be required.

  • RTEs are not simply the cellular midpoint between single-positive progenitor thymocytes and mature peripheral T cells, and this suggests that transit through this developmental stage is necessary.

  • Post-thymic maturation may be crucial for ensuring that RTEs are self tolerant or that they are fit to receive homeostatic signals.

Abstract

T cell maturation was once thought to occur entirely within the thymus. Now, evidence is mounting that the youngest peripheral T cells in both mice and humans comprise a distinct population from their more mature, yet still naive, counterparts. These cells, termed recent thymic emigrants (RTEs), undergo a process of post-thymic maturation that can be monitored at the levels of cell phenotype and immune function. Understanding this final maturation step in the process of generating useful and safe T cells is of clinical relevance, given that RTEs are over-represented in neonates and in adults recovering from lymphopenia. Post-thymic maturation may function to ensure T cell fitness and self tolerance.

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Figure 1: RTEs exhibit a distinct cell surface phenotype.

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Acknowledgements

This work was supported by US National Institutes of Health grants AI064318 (to P.J.F. with a supplement to D.W.H.) and DK091953 (to P.J.F.). The content is solely the responsibility of the authors and does not necessarily represent the official views of the US National Institute of Allergy and Infectious Diseases or the US National Institutes of Health.

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Authors and Affiliations

  1. Department of Immunology, University of Washington, Seattle, Washington, USA

    Pamela J. Fink & Deborah W. Hendricks

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Correspondence to Pamela J. Fink.

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Glossary

Recent thymic emigrants

T cells that have completed thymic development and have recently entered the lymphoid periphery. These young T cells undergo a maturation process that includes changes in function and cell surface phenotype.

Lymphoreplete

A lymphoid periphery that is relatively full of lymphocytes.

Lymphopenic

A lymphoid periphery that is depleted of lymphocytes.

Homeostasis

The controlled turnover of cell populations in which the balance between cell proliferation and cell death maintains constancy in the size of the lymphocyte pool.

Memory precursor CD8+ T cells

A subset of effector CD8+ T cells, defined as IL7RαhiKLRG1low that have an enhanced potential to become long-lived memory CD8+ T cells.

DNA methylation

A repressive epigenetic modification in which methyl groups are present on cytosine bases that are followed by guanine bases (CpGs). CpG-rich areas are typically found in gene promoter and other regulatory regions.

Anergy

A state of immune unresponsiveness. Anergic B and T cells do not respond fully to their cognate antigens.

Secondary lymphoid organs

Organs, including the spleen and lymph nodes, that support lymphocyte homeostasis, maturation and activation-induced differentiation.

Graft-versus-host disease

(GVHD). A disease that results from the immunological attack on target recipient organs or tissues (such as the skin or gut) by donor allogeneic T cells that are transferred along with the allograft (such as bone marrow, liver or gut allografts). GVHD occurs in graft recipients that are unable to eliminate the host-reactive donor T cells owing to immunosuppression, immunological immaturity or tolerance.

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Fink, P., Hendricks, D. Post-thymic maturation: young T cells assert their individuality. Nat Rev Immunol 11, 544–549 (2011). https://doi.org/10.1038/nri3028

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