Human blood MAIT cell subsets defined using MR1 tetramers
- Gherardin, Nicholas, Souter, Michael, Koay, Hui-Fern, Mangas, Kirstie, Seemann, Torsten, Stinear, Timothy, Eckle, Sidonia, Berzins, Stuart, d'Udekem, Yves, Konstantinov, Igor, Fairlie, David, Ritchie, David, Neeson, Paul, Pellicci, Daniel, Uldrich, Adam, McCluskey, James, Godfrey, Dale
- Authors: Gherardin, Nicholas , Souter, Michael , Koay, Hui-Fern , Mangas, Kirstie , Seemann, Torsten , Stinear, Timothy , Eckle, Sidonia , Berzins, Stuart , d'Udekem, Yves , Konstantinov, Igor , Fairlie, David , Ritchie, David , Neeson, Paul , Pellicci, Daniel , Uldrich, Adam , McCluskey, James , Godfrey, Dale
- Date: 2018
- Type: Text , Journal article
- Relation: Immunology and Cell Biology Vol. 96, no. 5 (2018), p. 507-525
- Full Text:
- Reviewed:
- Description: Mucosal-associated invariant T (MAIT) cells represent up to 10% of circulating human T cells. They are usually defined using combinations of non-lineage-specific (surrogate) markers such as anti-TRAV1-2, CD161, IL-18R
- Authors: Gherardin, Nicholas , Souter, Michael , Koay, Hui-Fern , Mangas, Kirstie , Seemann, Torsten , Stinear, Timothy , Eckle, Sidonia , Berzins, Stuart , d'Udekem, Yves , Konstantinov, Igor , Fairlie, David , Ritchie, David , Neeson, Paul , Pellicci, Daniel , Uldrich, Adam , McCluskey, James , Godfrey, Dale
- Date: 2018
- Type: Text , Journal article
- Relation: Immunology and Cell Biology Vol. 96, no. 5 (2018), p. 507-525
- Full Text:
- Reviewed:
- Description: Mucosal-associated invariant T (MAIT) cells represent up to 10% of circulating human T cells. They are usually defined using combinations of non-lineage-specific (surrogate) markers such as anti-TRAV1-2, CD161, IL-18R
Divergent SATB1 expression across human life span and tissue compartments
- Nüssing, Simone, Koay, Hui-Fern, Sant, Sneha, Loudovaris, Thomas, Mannering, Stuart, Lappas, Martha, d′Udekem, Yves, Konstantinov, Igor, Berzins, Stuart, Rimmelzwaan, Guus, Turner, Stephen, Clemens, Bridie, Godfrey, Dale, Nguyen, Thi, Kedzierska, Katherine
- Authors: Nüssing, Simone , Koay, Hui-Fern , Sant, Sneha , Loudovaris, Thomas , Mannering, Stuart , Lappas, Martha , d′Udekem, Yves , Konstantinov, Igor , Berzins, Stuart , Rimmelzwaan, Guus , Turner, Stephen , Clemens, Bridie , Godfrey, Dale , Nguyen, Thi , Kedzierska, Katherine
- Date: 2019
- Type: Text , Journal article
- Relation: Immunology and Cell Biology Vol. 97, no. (2019), p. 498-511
- Full Text:
- Reviewed:
- Description: Special AT-rich binding protein-1 (SATB1) is a global chromatin organizer capable of activating or repressing gene transcription in mice and humans. The role of SATB1 is pivotal for T-cell development, with SATB1-knockout mice being neonatally lethal, although the exact mechanism is unknown. Moreover, SATB1 is dysregulated in T-cell lymphoma and proposed to suppress transcription of the Pdcd1 gene, encoding the immune checkpoint programmed cell death protein 1 (PD-1). Thus, SATB1 expression in T-cell subsets across different tissue compartments in humans is of potential importance for targeting PD-1. Here, we comprehensively analyzed SATB1 expression across different human tissues and immune compartments by flow cytometry and correlated this with PD-1 expression. We investigated SATB1 protein levels in pediatric and adult donors and assessed expression dynamics of this chromatin organizer across different immune cell subsets in human organs, as well as in antigen-specific T cells directed against acute and chronic viral infections. Our data demonstrate that SATB1 expression in humans is the highest in T-cell progenitors in the thymus, and then becomes downregulated in mature T cells in the periphery. Importantly, SATB1 expression in peripheral mature T cells is not static and follows fine-tuned expression dynamics, which appear to be tissue- and antigen-dependent. Furthermore, SATB1 expression negatively correlates with PD-1 expression in virus-specific CD8 + T cells. Our study has implications for understanding the role of SATB1 in human health and disease and suggests an approach for modulating PD-1 in T cells, highly relevant to human malignancies or chronic viral infections.
- Authors: Nüssing, Simone , Koay, Hui-Fern , Sant, Sneha , Loudovaris, Thomas , Mannering, Stuart , Lappas, Martha , d′Udekem, Yves , Konstantinov, Igor , Berzins, Stuart , Rimmelzwaan, Guus , Turner, Stephen , Clemens, Bridie , Godfrey, Dale , Nguyen, Thi , Kedzierska, Katherine
- Date: 2019
- Type: Text , Journal article
- Relation: Immunology and Cell Biology Vol. 97, no. (2019), p. 498-511
- Full Text:
- Reviewed:
- Description: Special AT-rich binding protein-1 (SATB1) is a global chromatin organizer capable of activating or repressing gene transcription in mice and humans. The role of SATB1 is pivotal for T-cell development, with SATB1-knockout mice being neonatally lethal, although the exact mechanism is unknown. Moreover, SATB1 is dysregulated in T-cell lymphoma and proposed to suppress transcription of the Pdcd1 gene, encoding the immune checkpoint programmed cell death protein 1 (PD-1). Thus, SATB1 expression in T-cell subsets across different tissue compartments in humans is of potential importance for targeting PD-1. Here, we comprehensively analyzed SATB1 expression across different human tissues and immune compartments by flow cytometry and correlated this with PD-1 expression. We investigated SATB1 protein levels in pediatric and adult donors and assessed expression dynamics of this chromatin organizer across different immune cell subsets in human organs, as well as in antigen-specific T cells directed against acute and chronic viral infections. Our data demonstrate that SATB1 expression in humans is the highest in T-cell progenitors in the thymus, and then becomes downregulated in mature T cells in the periphery. Importantly, SATB1 expression in peripheral mature T cells is not static and follows fine-tuned expression dynamics, which appear to be tissue- and antigen-dependent. Furthermore, SATB1 expression negatively correlates with PD-1 expression in virus-specific CD8 + T cells. Our study has implications for understanding the role of SATB1 in human health and disease and suggests an approach for modulating PD-1 in T cells, highly relevant to human malignancies or chronic viral infections.
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