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Transcriptional signature of MAITs in LTBI (CD8+ or CD8-)

ABSTRACT: We applied a cell population transcriptomics strategy to sorted human memory CD8 T cells to define novel immune signatures of latent tuberculosis infection (LTBI) and understand the phenotype of tuberculosis (TB)-specific T cells. We found a 41-gene signature that could discriminate between memory CD8 T cells from healthy LTBI subjects and noninfected controls. The gene signature was dominated by genes known to be associated with mucosal associated invariant T cells (MAITs) and reflected the lower frequency of MAITs observed in individuals with LTBI. There was no evidence for a conventional CD8 T cell specific signature between the two cohorts. We therefore investigated the MAITs in more detail in these cohorts. Phenotyping based on Vα7.2 and CD161 expression and MR1 tetramers revealed 2 distinct populations of CD8+Vα7.2+CD161+ T cells: MR1 tetramer+ and MR1 tetramer−, both of which had a distinct gene expression profile compared to CD8 memory T cells. Transcriptomic analysis of LTBI vs. noninfected individuals did not reveal significant differences for MR1 tetramer+ cells. However, gene expression of MR1 tetramer− cells showed a very different profile with large inter-individual diversity and a TB-specific signature. This was further strengthened by a more diverse TCR-α and -β repertoire of MR1 tetramer− cells as compared to MR1 tetramer+. Thus, cell population transcriptomics revealed a dominant MAIT signature in CD8 memory T cells that upon detailed investigation provided novel insights into the phenotype of different MAIT populations implicated in tuberculosis.

ORGANISM(S): Homo sapiens

PROVIDER: GSE132931 | GEO | 2020/05/13

REPOSITORIES: GEO

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Transcriptional signature of MAITs in LTBI (memory CD8 T cells and subsets of TRAV1-2+CD161+ MAITs)

Project description:We applied a cell population transcriptomics strategy to sorted human memory CD8 T cells to define novel immune signatures of latent tuberculosis infection (LTBI) and understand the phenotype of tuberculosis (TB)-specific T cells. We found a 41-gene signature that could discriminate between memory CD8 T cells from healthy LTBI subjects and noninfected controls. The gene signature was dominated by genes known to be associated with mucosal associated invariant T cells (MAITs) and reflected the lower frequency of MAITs observed in individuals with LTBI. There was no evidence for a conventional CD8 T cell specific signature between the two cohorts. We therefore investigated the MAITs in more detail in these cohorts. Phenotyping based on Vα7.2 and CD161 expression and MR1 tetramers revealed 2 distinct populations of CD8+Vα7.2+CD161+ T cells: MR1 tetramer+ and MR1 tetramer−, both of which had a distinct gene expression profile compared to CD8 memory T cells. Transcriptomic analysis of LTBI vs. noninfected individuals did not reveal significant differences for MR1 tetramer+ cells. However, gene expression of MR1 tetramer− cells showed a very different profile with large inter-individual diversity and a TB-specific signature. This was further strengthened by a more diverse TCR-α and -β repertoire of MR1 tetramer− cells as compared to MR1 tetramer+. Thus, cell population transcriptomics revealed a dominant MAIT signature in CD8 memory T cells that upon detailed investigation provided novel insights into the phenotype of different MAIT populations implicated in tuberculosis.

2020-05-13 | GSE132932 | GEO

Transcriptional signature of MAITs in LTBI

2020-05-13 | GSE132790 | GEO

Microarray expression profiling of NKT and MAIT subsets in different organs of B6-MAIT/CAST mice.

Project description:MAIT cells (MAITs) represent an abundant T lymphocyte subset with unique specificity for microbial metabolites presented by the MHC-1b molecule, MR1. MAIT conservation along evolution indicates important, non-redundant functions, but their low frequency in mice has hampered their detailed characterization. Here, we performed a transcriptomic analysis of murine MAITs in comparison with NKT subsets and with mainstream T cells in spleen and peripheral organs of B6-MAIT/CAST mice expressing a Rorc-GFP transgene. MAIT and NKT cells have been FACS-sorted after tetramer staining (MR1:5-OP-RU Tet+ for MAIT, CD1d:PBS57Tet+ for NKT), and 1/17 subsetting based on the expression of Rorc.

2018-12-03 | E-MTAB-7133 | biostudies-arrayexpress

Transcriptional signature of MAITs in LTBI (CD8+ or CD8-)

Project description:Transcriptional signature of MAITs in LTBI (CD8+ or CD8-)

| PRJNA549485 | ENA

Transcriptional signature of MAITs in LTBI (memory CD8 T cells and subsets of TRAV1-2+CD161+ MAITs)

Project description:Transcriptional signature of MAITs in LTBI (memory CD8 T cells and subsets of TRAV1-2+CD161+ MAITs)

| PRJNA549484 | ENA

Transcriptional signature of MAITs in LTBI

Project description:Transcriptional signature of MAITs in LTBI

| PRJNA549010 | ENA

Transcriptome of activated human and mouse MAIT cells

Project description:We sought to describe in detail the consequences of MAIT cell activation using a transcriptomic approach to define the basic transcriptome of a MAIT cell in both humans and mice and to determine how this is modulated by activation. Fresh human peripheral blood cells were obtained from three donors. These were cultured for 6 hours with (‘stimulated’) or without (‘unstimulated’) 10 nM 5-OP-RU, magnetically enriched on MR1-tetramer+ cells, and flow-sorted for RNA sequencing of live CD3+TCR Valpha7.2+ MR1-5-OP-RU tetramer+ MAIT cells, and of unstimulated naïve live CD8+CD45RA+ T cells as a comparator cell type. For the murine samples we included within the same sequencing experiment live pulmonary CD3+45.2+19-MR1-5-OP-RU tetramer+ MAIT cells which were magnetically enriched and flow-sorted from the lungs of mice 7 days after infection with 1x104 CFU L. longbeachae (‘acute’), or at least 12 weeks post infection (‘resolution’) or 7 days after a second intranasal infection with 2x104 CFU L. longbeachae in mice that had recovered from infection 12 weeks previously (‘reinfection’). Live CD3+CD45.2+CD19-CD8+CD44-CD62L+ naïve T cells from uninfected mice were used as a comparator cell type.

2019-09-10 | GSE123805 | GEO

Transcriptomic profile of circulating memory T cells can differentiate between latent tuberculosis individuals and healthy controls

Project description:Tuberculosis (TB) is responsible for the majority of mortality and morbidity associated with infectious diseases worldwide. The characterization of exact molecular components of immune response associated with protection against TB may help design more effective therapeutic interventions. In this study, we aimed to characterize the immune signature of memory T cells associated with latent infection with Mycobacterium tuberculosis. Transcriptomic profiling using RNA sequencing was performed on memory CD4 and CD8 T cells isolated from individuals with latent tuberculosis, as well as from tuberculosis negative healthy controls. Overall, we found specific gene signatures in each cell subset that could successfully discriminate between individuals with latent tuberculosis and healthy controls.

2019-06-12 | GSE84445 | GEO

Transcriptomic profile of circulating memory CD8 T cells can differentiate between latent tuberculosis individuals and healthy controls

Project description:Tuberculosis (TB) is responsible for the majority of mortality and morbidity associated with infectious diseases worldwide. The characterization of exact molecular components of immune response associated with protection against TB may help design more effective therapeutic interventions. In this study, we aimed to characterize the immune signature of memory T cells associated with latent infection with Mycobacterium tuberculosis. Transcriptomic profiling using RNA sequencing was performed on memory CD8 T cells isolated from individuals with latent tuberculosis, as well as from tuberculosis negative healthy controls. Overall, we found specific gene signatures in each cell subset that could successfully discriminate between individuals with latent tuberculosis and healthy controls.

2020-05-26 | GSE99374 | GEO

HLADR expression marks recently divided memory CD4 T cells in latent tuberculosis infected subjects upon in vitro stimulation with Mycobacterium tuberculosis antigens

Project description:Upon antigen encounter, T cells can rapidly divide and form short-lived effector cells which plays an important role fighting an active infection. However, little is known about the molecular markers that distinguish such effector cells from other T cell populations in humans. Due to previous exposure with Mycobacterium tuberculosis (Mtb), we expect latent tuberculosis infected (LTBI) subjects to have Mtb-specific memory CD4 T cells that are capable of rapid expansion upon antigen re-encounter. To investigate this further we designed an in vitro MTP-AE (Memory T cell Proliferation upon Antigen Exposure) assay to track and isolate proliferated CD4 T cells in response to antigen stimulation. PBMCs from LTBI subjects were cultured with the MTB300 (Mtb specific peptide pool, PMID: 27409590) for 8 days before sorting for HLADR+ vs HLADR- and divided vs undivided CD4 T cells. We found that HLADR is a marker of recently divided memory CD4 T cells and that differentially expessed genes in HLADR+/recently divided cells were enriched for cytotoxic markers and cytokines compared to HLADR-/undivided cells.

2021-05-11 | GSE162725 | GEO

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