Dataset Information

The human V?2+ T-cell compartment comprises distinct innate-like V?9+ and adaptive V?9- subsets.

ABSTRACT: V?2+ T cells form the predominant human ?? T-cell population in peripheral blood and mediate T-cell receptor (TCR)-dependent anti-microbial and anti-tumour immunity. Here we show that the V?2+ compartment comprises both innate-like and adaptive subsets. V?9+ V?2+ T cells display semi-invariant TCR repertoires, featuring public V?9 TCR sequences equivalent in cord and adult blood. By contrast, we also identify a separate, V?9- V?2+ T-cell subset that typically has a CD27hiCCR7+CD28+IL-7R?+ naive-like phenotype and a diverse TCR repertoire, however in response to viral infection, undergoes clonal expansion and differentiation to a CD27loCD45RA+CX3CR1+granzymeA/B+ effector phenotype. Consistent with a function in solid tissue immunosurveillance, we detect human intrahepatic V?9- V?2+ T cells featuring dominant clonal expansions and an effector phenotype. These findings redefine human ?? T-cell subsets by delineating the V?2+ T-cell compartment into innate-like (V?9+) and adaptive (V?9-) subsets, which have distinct functions in microbial immunosurveillance.

SUBMITTER: Davey MS

PROVIDER: S-EPMC5932074 | biostudies-literature | 2018 May

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

The human Vδ2+ T-cell compartment comprises distinct innate-like Vγ9+ and adaptive Vγ9- subsets.

Davey Martin S MS Willcox Carrie R CR Hunter Stuart S Kasatskaya Sofya A SA Remmerswaal Ester B M EBM Salim Mahboob M Mohammed Fiyaz F Bemelman Frederike J FJ Chudakov Dmitriy M DM Oo Ye H YH Willcox Benjamin E BE

Nature communications 20180502 1

Vδ2+ T cells form the predominant human γδ T-cell population in peripheral blood and mediate T-cell receptor (TCR)-dependent anti-microbial and anti-tumour immunity. Here we show that the Vδ2+ compartment comprises both innate-like and adaptive subsets. Vγ9+ Vδ2+ T cells display semi-invariant TCR repertoires, featuring public Vγ9 TCR sequences equivalent in cord and adult blood. By contrast, we also identify a separate, Vγ9- Vδ2+ ...[more]

PMID: 29720665

Similar Datasets

Project description:Standard chemotherapy for acute myeloid leukemia (AML) targets proliferative cells and efficiently induces complete remission; however, many patients relapse and die of their disease. Relapse is caused by leukemia stem cells (LSC), the cells with self-renewal capacity. Self-renewal and proliferation are separate functions in normal hematopoietic stem cells (HSC) in steady-state conditions. If these functions are also separate functions in LSCs, then antiproliferative therapies may fail to target self-renewal, allowing for relapse. We investigated whether proliferation and self-renewal are separate functions in LSCs as they often are in HSCs. Distinct transcriptional profiles within LSCs of Mll-AF9/NRASG12V murine AML were identified using single-cell RNA sequencing. Single-cell qPCR revealed that these genes were also differentially expressed in primary human LSCs and normal human HSPCs. A smaller subset of these genes was upregulated in LSCs relative to HSPCs; this subset of genes constitutes "LSC-specific" genes in human AML. To assess the differences between these profiles, we identified cell surface markers, CD69 and CD36, whose genes were differentially expressed between these profiles. In vivo mouse reconstitution assays resealed that only CD69High LSCs were capable of self-renewal and were poorly proliferative. In contrast, CD36High LSCs were unable to transplant leukemia but were highly proliferative. These data demonstrate that the transcriptional foundations of self-renewal and proliferation are distinct in LSCs as they often are in normal stem cells and suggest that therapeutic strategies that target self-renewal, in addition to proliferation, are critical to prevent relapse and improve survival in AML. SIGNIFICANCE: These findings define and functionally validate a self-renewal gene profile of leukemia stem cells at the single-cell level and demonstrate that self-renewal and proliferation are distinct in AML. GRAPHICAL ABSTRACT: http://cancerres.aacrjournals.org/content/canres/80/3/458/F1.large.jpg.

Dataset Information

The human V?2+ T-cell compartment comprises distinct innate-like V?9+ and adaptive V?9- subsets.

Publications

The human Vδ2<sup>+</sup> T-cell compartment comprises distinct innate-like Vγ9<sup>+</sup> and adaptive Vγ9<sup>-</sup> subsets.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets