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The peripheral differentiation of human natural killer T cells

Liu, Jie, Hill, Brenna J, Darko, Sam, Song, Kaimei, Quigley, Máire F, Asher, Tedi E, Morita, Yohei, Greenaway, Hui Y, Venturi, Vanessa, Douek, Daniel C, Davenport, Miles P, Price, David A and Roederer, Mario 2019. The peripheral differentiation of human natural killer T cells. Immunology and Cell Biology 97 (6) , pp. 586-596. 10.1111/imcb.12248

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Abstract

The peripheral maturation of human CD1d‐restricted natural killer T (NKT) cells has not been well described. In this study, we identified four major subsets of NKT cells in adults, distinguished by the expression of CD4, CD8 and CCR5. Phenotypic analysis suggested a hierarchical pattern of differentiation, whereby immature CD4+CD8−CCR5− cells progressed to an intermediate CD4+CD8−CCR5+ stage, which remained less differentiated than the CD4−CD8− and CD4−CD8+ subsets, both of which expressed CCR5. This interpretation was supported by functional data, including clonogenic potential and cytokine secretion profiles, as well as T‐cell receptor (TCR) excision circle analysis. Moreover, conventional and high‐throughput sequencing of the corresponding TCR repertoires demonstrated significant clonotypic overlap within individuals, especially between the more differentiated CD4−CD8− and CD4−CD8+ subsets. Collectively, these results mapped a linear differentiation pathway across the post‐thymic landscape of human CD1d‐restricted NKT cells.

Item Type: Article
Date Type: Publication
Status: Published
Schools: Medicine
Publisher: Nature Publishing Group
ISSN: 0818-9641
Funders: Wellcome Trust
Date of First Compliant Deposit: 9 April 2019
Date of Acceptance: 11 March 2019
Last Modified: 17 Jul 2019 11:27
URI: http://orca-mwe.cf.ac.uk/id/eprint/121617

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