Tracking immunodynamics by identification of S-G2/M-phase T cells in human peripheral blood

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Tracking immunodynamics by identification of S-G2/M-phase T cells in human peripheral blood. / Munoz-Ruiz, Miguel; Pujol-Autonell, Irma; Rhys, Hefin; Long, Heather; Greco, Maria; Peakman, Mark; Tree, Tim; Hayday, Adrian; Di Rosa, Francesca.

In: Journal of Autoimmunity, 12.05.2020.

Research output: Contribution to journalArticlepeer-review

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APA

Munoz-Ruiz, M., Pujol-Autonell, I., Rhys, H., Long, H., Greco, M., Peakman, M., Tree, T., Hayday, A., & Di Rosa, F. (2020). Tracking immunodynamics by identification of S-G2/M-phase T cells in human peripheral blood. Journal of Autoimmunity, [102466]. https://doi.org/10.1016/j.jaut.2020.102466

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Author

Munoz-Ruiz, Miguel ; Pujol-Autonell, Irma ; Rhys, Hefin ; Long, Heather ; Greco, Maria ; Peakman, Mark ; Tree, Tim ; Hayday, Adrian ; Di Rosa, Francesca. / Tracking immunodynamics by identification of S-G2/M-phase T cells in human peripheral blood. In: Journal of Autoimmunity. 2020.

Bibtex

@article{f26640193d174659935acfefda2683f6,
title = "Tracking immunodynamics by identification of S-G2/M-phase T cells in human peripheral blood",
abstract = "The readily availability of human blood makes it the first choice for immuno-monitoring. However, this has been largely confined to static metrics, particularly resting T cell phenotypes. Conversely, dynamic assessments have mostly relied on cell stimulation in vitro which is subject to multiple variables. Here, immunodynamic insights from the peripheral blood are shown to be obtainable by applying a revised approach to cell-cycle analysis. Specifically, refined flow cytometric protocols were employed, assuring the reliable quantification of T cells in the S-G2/M phases of the cell-cycle (collectively termed “T Double S” for T cells in S-phase in Sanguine: in short “TDS” cells) that were neither excluded from conventional lymphocyte gates, nor confused with cell doublets artefactually displaying high DNA-content. To illustrate the nature of TDS cells, and their relationship to different immunodynamic scenarios, we examined them in healthy donors (HD); infectious mononucleosis (IM) patients versus asymptomatic EBV+ carriers; and recently-diagnosed T1D patients. TDS were reproducibly more abundant among CD8+ T cells and a defined subset of T-regulatory CD4+ T cells, and were substantially increased in IM and a subset of T1D patients. Of note, islet antigen-reactive TDS cell frequencies were associated with an aggressive T cell effector phenotype, suggesting that peripheral blood can reflect immune events within tissues in T1D, and possibly in other organ-specific autoimmune diseases. Our results suggest that tracking TDS cells may provide a widely applicable means of gaining insight into ongoing immune response dynamics in a variety of settings, including tissue immunopathologies where the peripheral blood has often not been considered insightful.",
keywords = "Epstein-Barr virus, Immunity, type 1 diabetes, immuno-monitoring, CD8 T cells",
author = "Miguel Munoz-Ruiz and Irma Pujol-Autonell and Hefin Rhys and Heather Long and Maria Greco and Mark Peakman and Tim Tree and Adrian Hayday and {Di Rosa}, Francesca",
year = "2020",
month = may,
day = "12",
doi = "10.1016/j.jaut.2020.102466",
language = "English",
journal = "Journal of Autoimmunity",
issn = "0896-8411",
publisher = "Elsevier",

}

RIS

TY - JOUR

T1 - Tracking immunodynamics by identification of S-G2/M-phase T cells in human peripheral blood

AU - Munoz-Ruiz, Miguel

AU - Pujol-Autonell, Irma

AU - Rhys, Hefin

AU - Long, Heather

AU - Greco, Maria

AU - Peakman, Mark

AU - Tree, Tim

AU - Hayday, Adrian

AU - Di Rosa, Francesca

PY - 2020/5/12

Y1 - 2020/5/12

N2 - The readily availability of human blood makes it the first choice for immuno-monitoring. However, this has been largely confined to static metrics, particularly resting T cell phenotypes. Conversely, dynamic assessments have mostly relied on cell stimulation in vitro which is subject to multiple variables. Here, immunodynamic insights from the peripheral blood are shown to be obtainable by applying a revised approach to cell-cycle analysis. Specifically, refined flow cytometric protocols were employed, assuring the reliable quantification of T cells in the S-G2/M phases of the cell-cycle (collectively termed “T Double S” for T cells in S-phase in Sanguine: in short “TDS” cells) that were neither excluded from conventional lymphocyte gates, nor confused with cell doublets artefactually displaying high DNA-content. To illustrate the nature of TDS cells, and their relationship to different immunodynamic scenarios, we examined them in healthy donors (HD); infectious mononucleosis (IM) patients versus asymptomatic EBV+ carriers; and recently-diagnosed T1D patients. TDS were reproducibly more abundant among CD8+ T cells and a defined subset of T-regulatory CD4+ T cells, and were substantially increased in IM and a subset of T1D patients. Of note, islet antigen-reactive TDS cell frequencies were associated with an aggressive T cell effector phenotype, suggesting that peripheral blood can reflect immune events within tissues in T1D, and possibly in other organ-specific autoimmune diseases. Our results suggest that tracking TDS cells may provide a widely applicable means of gaining insight into ongoing immune response dynamics in a variety of settings, including tissue immunopathologies where the peripheral blood has often not been considered insightful.

AB - The readily availability of human blood makes it the first choice for immuno-monitoring. However, this has been largely confined to static metrics, particularly resting T cell phenotypes. Conversely, dynamic assessments have mostly relied on cell stimulation in vitro which is subject to multiple variables. Here, immunodynamic insights from the peripheral blood are shown to be obtainable by applying a revised approach to cell-cycle analysis. Specifically, refined flow cytometric protocols were employed, assuring the reliable quantification of T cells in the S-G2/M phases of the cell-cycle (collectively termed “T Double S” for T cells in S-phase in Sanguine: in short “TDS” cells) that were neither excluded from conventional lymphocyte gates, nor confused with cell doublets artefactually displaying high DNA-content. To illustrate the nature of TDS cells, and their relationship to different immunodynamic scenarios, we examined them in healthy donors (HD); infectious mononucleosis (IM) patients versus asymptomatic EBV+ carriers; and recently-diagnosed T1D patients. TDS were reproducibly more abundant among CD8+ T cells and a defined subset of T-regulatory CD4+ T cells, and were substantially increased in IM and a subset of T1D patients. Of note, islet antigen-reactive TDS cell frequencies were associated with an aggressive T cell effector phenotype, suggesting that peripheral blood can reflect immune events within tissues in T1D, and possibly in other organ-specific autoimmune diseases. Our results suggest that tracking TDS cells may provide a widely applicable means of gaining insight into ongoing immune response dynamics in a variety of settings, including tissue immunopathologies where the peripheral blood has often not been considered insightful.

KW - Epstein-Barr virus

KW - Immunity

KW - type 1 diabetes

KW - immuno-monitoring

KW - CD8 T cells

U2 - 10.1016/j.jaut.2020.102466

DO - 10.1016/j.jaut.2020.102466

M3 - Article

JO - Journal of Autoimmunity

JF - Journal of Autoimmunity

SN - 0896-8411

M1 - 102466

ER -