The full spectrum of human naive T cells
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.
Evidence is increasing that naive T cells are heterogeneous in phenotype, function, dynamics and differentiation status. Here, van den Broek et al. provide a revised view of the naive T cell compartment and then discuss the implications for ageing, neonatal immunity and T cell reconstitution following haematopoietic stem cell transplantation.
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.
Nature Reviews Immunology thanks R. Kedl and the other anonymous reviewer(s), for their contribution to the peer review of this work.
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.
The authors declare no competing interests.
The condition of having an abnormally low level of lymphocytes in the circulation.
(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.
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.
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.
Naive T cells that have matured in secondary lymphoid organs following thymic egress and are no longer recent thymic emigrants.
(TRECs). Small, stable circles of DNA excised during T cell receptor gene rearrangement in the thymus.
A measure of diversity that takes into account the number of clones present, as well as the relative abundance of each clone.
The extent to which a repertoire deviates from a situation where all clones occur equally frequently.
The amount of T cells that successfully exit the thymus into the periphery after intrathymic selection.
(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.
- 23.Vrisekoop, N. T-cell dynamics in healthy and HIV-infected individuals Ch. 7 Thesis, Utrecht Univ. (2007).Google Scholar
- 34.Moskowitz, D. M. et al. Epigenomics of human CD8 T cell differentiation and aging. Sci. Immunol. 2, eaag0192 (2017).Google Scholar
- 48.Thome, J. J. et al. Longterm maintenance of human naive T cells through in situ homeostasis in lymphoid tissue sites. Sci. Immunol. 1, eaah6506 (2016). This study reveals long-term maintenance of human naive T cells in lymphoid tissues with site-specific clonal expansions of naive T cells. PubMedPubMedCentralCrossRefGoogle Scholar
- 50.Centers for Disease Control and Prevention. Estimates of deaths associated with seasonal influenza—United States, 1976–2007. MMWR Morb. Mortal. Wkly Rep. 59, 1057–1062 (2010).Google Scholar
- 60.Haynes, L., Eaton, S. M., Burns, E. M., Randall, T. D. & Swain, S. L. CD4 T cell memory derived from young naive cells functions well into old age, but memory generated from aged naive cells functions poorly. Proc. Natl Acad. Sci. USA 100, 15053–15058 (2003).PubMedPubMedCentralCrossRefGoogle Scholar
- 69.Galindo-Albarran, A. O. et al. CD8+ T cells from human neonates are biased toward an innate immune response. Cell Rep. 17, 2151–2160 (2016). This study demonstrates that neonatal CD8 T cells have a distinct epigenetic landscape that is biased towards an innate immune response. PubMedCrossRefGoogle Scholar
- 132.Saukkonen, J. J., Kornfeld, H. & Berman, J. S. Expansion of a CD8+CD28- cell population in the blood and lung of HIV-positive patients. J. Acquir. Immune Def. Syndr. 6, 1194–1204 (1993).Google Scholar