The peripheral differentiation of human natural killer T cells

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 different...

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Bibliographic Details
Published in:	Immunology and cell biology Vol. 97; no. 6; pp. 586 - 596
Main Authors:	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, Roederer, Mario
Format:	Journal Article
Language:	English
Published:	United States Blackwell Science Ltd 01-07-2019 John Wiley and Sons Inc
Subjects:	Antigens, CD1d - metabolism CCR5 protein CD1d antigen CD4 antigen CD4 Antigens - metabolism CD8 antigen CD8 Antigens - metabolism Cell Differentiation Cells, Cultured Clone Cells Cytokines - metabolism Flow Cytometry High-Throughput Nucleotide Sequencing Humans Immunophenotyping Lymphocyte Subsets - immunology Lymphocytes T Natural killer cells Natural Killer T-Cells - immunology NKT cell Original Receptors, Antigen, T-Cell - genetics Receptors, CCR5 - metabolism T cell receptors TCR Thymus TREC T‐cell differentiation TCR T-cell differentiation TREC NKT cell
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Summary:	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. We used phenotypic, functional and molecular techniques to map a linear differentiation pathway across the post‐thymic landscape of human CD1d‐restricted NKT cells.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 Equal contributors.
ISSN:	0818-9641 1440-1711
DOI:	10.1111/imcb.12248