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The peripheral differentiation of human natural killer T cells

2019/03/16 by Jie Liu, Brenna J. Hill, Brenna J Hill +18
Immunology and Microbiology · Medicine · #Immune Cell Function and Interaction #T-cell and B-cell Immunology #CAR-T cell therapy research

paper · pdf · doi:10.1111/imcb.12248

Abstract

Abstract The peripheral maturation of human CD 1d‐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 CD 4, CD 8 and CCR 5. Phenotypic analysis suggested a hierarchical pattern of differentiation, whereby immature CD 4 + CD 8 − CCR 5 − cells progressed to an intermediate CD 4 + CD 8 − CCR 5 + stage, which remained less differentiated than the CD 4 − CD 8 − and CD 4 − CD 8 + subsets, both of which expressed CCR 5. 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 CD 4 − CD 8 − and CD 4 − CD 8 + subsets. Collectively, these results mapped a linear differentiation pathway across the post‐thymic landscape of human CD 1d‐restricted NKT cells.

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