A high-dimensional cytometry atlas of peripheral blood over the human life span
- Jalali, Sedigheh, Harpur, Christopher, Piers, Adam, Auladell, Maria, Perriman, Louis, Li, Shuo, An, Kim, Anderson, Jeremy, Berzins, Stuart, Licciardi, Paul, Ashhurst, Thomas, Konstantinov, Igor, Pellicci, Daniel
- Authors: Jalali, Sedigheh , Harpur, Christopher , Piers, Adam , Auladell, Maria , Perriman, Louis , Li, Shuo , An, Kim , Anderson, Jeremy , Berzins, Stuart , Licciardi, Paul , Ashhurst, Thomas , Konstantinov, Igor , Pellicci, Daniel
- Date: 2022
- Type: Text , Journal article
- Relation: Immunology and Cell Biology Vol. 100, no. 10 (2022), p. 805-821
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- Description: Age can profoundly affect susceptibility to a broad range of human diseases. Children are more susceptible to some infectious diseases such as diphtheria and pertussis, while in others, such as coronavirus disease 2019 and hepatitis A, they are more protected compared with adults. One explanation is that the composition of the immune system is a major contributing factor to disease susceptibility and severity. While most studies of the human immune system have focused on adults, how the immune system changes after birth remains poorly understood. Here, using high-dimensional spectral flow cytometry and computational methods for data integration, we analyzed more than 50 populations of immune cells in the peripheral blood, generating an immune cell atlas that defines the healthy human immune system from birth up to 75 years of age. We focused our efforts on children under 18 years old, revealing major changes in immune cell populations after birth and in children of schooling age. Specifically, CD4+ T effector memory cells, V
- Authors: Jalali, Sedigheh , Harpur, Christopher , Piers, Adam , Auladell, Maria , Perriman, Louis , Li, Shuo , An, Kim , Anderson, Jeremy , Berzins, Stuart , Licciardi, Paul , Ashhurst, Thomas , Konstantinov, Igor , Pellicci, Daniel
- Date: 2022
- Type: Text , Journal article
- Relation: Immunology and Cell Biology Vol. 100, no. 10 (2022), p. 805-821
- Full Text:
- Reviewed:
- Description: Age can profoundly affect susceptibility to a broad range of human diseases. Children are more susceptible to some infectious diseases such as diphtheria and pertussis, while in others, such as coronavirus disease 2019 and hepatitis A, they are more protected compared with adults. One explanation is that the composition of the immune system is a major contributing factor to disease susceptibility and severity. While most studies of the human immune system have focused on adults, how the immune system changes after birth remains poorly understood. Here, using high-dimensional spectral flow cytometry and computational methods for data integration, we analyzed more than 50 populations of immune cells in the peripheral blood, generating an immune cell atlas that defines the healthy human immune system from birth up to 75 years of age. We focused our efforts on children under 18 years old, revealing major changes in immune cell populations after birth and in children of schooling age. Specifically, CD4+ T effector memory cells, V
A three-stage intrathymic development pathway for the mucosal-associated invariant T cell lineage
- Koay, Hui-Fern, Gherardin, Nicholas, Enders, Anselm, Loh, Liyen, Mackay, Laura, Almeida, Catarina, Russ, Brendan, Nold-Petry, Claudia, Nold, Marcel, Bedoui, Sammy, Chen, Zhenjun, Corbett, Alexandra, Eckle, Sidonia, Meehan, Bronwyn, d'Udekem, Yves, Konstantinov, Igor, Lappas, Martha, Liu, Ligong, Goodnow, Chris, Fairlie, David, Rossjohn, Jamie, Chong, Mark, Kedzierska, Katherine, Berzins, Stuart, Belz, Gabrielle, McCluskey, James, Uldrich, Adam, Godfrey, Dale, Pellicci, Daniel
- Authors: Koay, Hui-Fern , Gherardin, Nicholas , Enders, Anselm , Loh, Liyen , Mackay, Laura , Almeida, Catarina , Russ, Brendan , Nold-Petry, Claudia , Nold, Marcel , Bedoui, Sammy , Chen, Zhenjun , Corbett, Alexandra , Eckle, Sidonia , Meehan, Bronwyn , d'Udekem, Yves , Konstantinov, Igor , Lappas, Martha , Liu, Ligong , Goodnow, Chris , Fairlie, David , Rossjohn, Jamie , Chong, Mark , Kedzierska, Katherine , Berzins, Stuart , Belz, Gabrielle , McCluskey, James , Uldrich, Adam , Godfrey, Dale , Pellicci, Daniel
- Date: 2016
- Type: Text , Journal article
- Relation: Nature Immunology Vol. 17, no. 11 (2016), p. 1300-1311
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- Description: Mucosal-associated invariant T cells (MAIT cells) detect microbial vitamin B2 derivatives presented by the antigen-presenting molecule MR1. Here we defined three developmental stages and checkpoints for the MAIT cell lineage in humans and mice. Stage 1 and stage 2 MAIT cells predominated in thymus, while stage 3 cells progressively increased in abundance extrathymically. Transition through each checkpoint was regulated by MR1, whereas the final checkpoint that generated mature functional MAIT cells was controlled by multiple factors, including the transcription factor PLZF and microbial colonization. Furthermore, stage 3 MAIT cell populations were expanded in mice deficient in the antigen-presenting molecule CD1d, suggestive of a niche shared by MAIT cells and natural killer T cells (NKT cells). Accordingly, this study maps the developmental pathway and checkpoints that control the generation of functional MAIT cells.
- Authors: Koay, Hui-Fern , Gherardin, Nicholas , Enders, Anselm , Loh, Liyen , Mackay, Laura , Almeida, Catarina , Russ, Brendan , Nold-Petry, Claudia , Nold, Marcel , Bedoui, Sammy , Chen, Zhenjun , Corbett, Alexandra , Eckle, Sidonia , Meehan, Bronwyn , d'Udekem, Yves , Konstantinov, Igor , Lappas, Martha , Liu, Ligong , Goodnow, Chris , Fairlie, David , Rossjohn, Jamie , Chong, Mark , Kedzierska, Katherine , Berzins, Stuart , Belz, Gabrielle , McCluskey, James , Uldrich, Adam , Godfrey, Dale , Pellicci, Daniel
- Date: 2016
- Type: Text , Journal article
- Relation: Nature Immunology Vol. 17, no. 11 (2016), p. 1300-1311
- Full Text:
- Reviewed:
- Description: Mucosal-associated invariant T cells (MAIT cells) detect microbial vitamin B2 derivatives presented by the antigen-presenting molecule MR1. Here we defined three developmental stages and checkpoints for the MAIT cell lineage in humans and mice. Stage 1 and stage 2 MAIT cells predominated in thymus, while stage 3 cells progressively increased in abundance extrathymically. Transition through each checkpoint was regulated by MR1, whereas the final checkpoint that generated mature functional MAIT cells was controlled by multiple factors, including the transcription factor PLZF and microbial colonization. Furthermore, stage 3 MAIT cell populations were expanded in mice deficient in the antigen-presenting molecule CD1d, suggestive of a niche shared by MAIT cells and natural killer T cells (NKT cells). Accordingly, this study maps the developmental pathway and checkpoints that control the generation of functional MAIT cells.
Altered populations of unconventional T Cell lineages in patients with Langerhans Cell Histiocytosis
- Mitchell, Jenée, Kvedaraite, Egle, von Bahr Greenwood, Tatiana, Henter, Jan-Inge, Pellicci, Daniel, Berzins, Stuart, Kannourakis, George
- Authors: Mitchell, Jenée , Kvedaraite, Egle , von Bahr Greenwood, Tatiana , Henter, Jan-Inge , Pellicci, Daniel , Berzins, Stuart , Kannourakis, George
- Date: 2018
- Type: Text , Journal article
- Relation: Scientific Reports Vol. 8, no. 1 (2018), p. 1-13
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- Description: Langerhans cell histiocytosis (LCH) lesions are defined by the presence of CD1a+/CD207+ myeloid cells, but many other immune cells are present including unconventional T cells, which have powerful immunoregulatory functions. Unconventional T cell lineages include mucosal-associated invariant T (MAIT) cells, type I natural killer T (NKT) cells and gamma-delta (γδ) T cells, which are associated with many inflammatory conditions, although their importance has not been studied in LCH. We characterized their phenotype and function in blood and lesions from patients with LCH, and identified a deficiency in MAIT cell frequency and abnormalities in the subset distributions of γδ T cells and NKT cells. Such abnormalities are associated with immune dysregulation in other disease settings and are therefore potentially important in LCH. Our study is the first to recognize alterations to MAIT cell proportions in patients with LCH. This finding along with other abnormalities identified amongst unconventional T cells could potentially influence the onset and progression of LCH, thereby highlighting potential targets for new immune based therapies.
Altered populations of unconventional T Cell lineages in patients with Langerhans Cell Histiocytosis
- Authors: Mitchell, Jenée , Kvedaraite, Egle , von Bahr Greenwood, Tatiana , Henter, Jan-Inge , Pellicci, Daniel , Berzins, Stuart , Kannourakis, George
- Date: 2018
- Type: Text , Journal article
- Relation: Scientific Reports Vol. 8, no. 1 (2018), p. 1-13
- Full Text:
- Reviewed:
- Description: Langerhans cell histiocytosis (LCH) lesions are defined by the presence of CD1a+/CD207+ myeloid cells, but many other immune cells are present including unconventional T cells, which have powerful immunoregulatory functions. Unconventional T cell lineages include mucosal-associated invariant T (MAIT) cells, type I natural killer T (NKT) cells and gamma-delta (γδ) T cells, which are associated with many inflammatory conditions, although their importance has not been studied in LCH. We characterized their phenotype and function in blood and lesions from patients with LCH, and identified a deficiency in MAIT cell frequency and abnormalities in the subset distributions of γδ T cells and NKT cells. Such abnormalities are associated with immune dysregulation in other disease settings and are therefore potentially important in LCH. Our study is the first to recognize alterations to MAIT cell proportions in patients with LCH. This finding along with other abnormalities identified amongst unconventional T cells could potentially influence the onset and progression of LCH, thereby highlighting potential targets for new immune based therapies.
High CD26 and low CD94 expression identifies an IL-23 responsive Vδ2+ T Cell subset with a MAIT cell-like transcriptional profile
- Wragg, Kathleen, Tan, Hyon, Kristensen, Anne, Nguyen-Robertson, Catriona, Kelleher, Anthony, Parsons, Matthew, Wheatley, Adam, Berzins, Stuart, Pellicci, Daniel, Kent, Stephen, Juno, Jennifer
- Authors: Wragg, Kathleen , Tan, Hyon , Kristensen, Anne , Nguyen-Robertson, Catriona , Kelleher, Anthony , Parsons, Matthew , Wheatley, Adam , Berzins, Stuart , Pellicci, Daniel , Kent, Stephen , Juno, Jennifer
- Date: 2020
- Type: Text , Journal article
- Relation: Cell Reports Vol. 31, no. 11 (2020), p.
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- Description: Vδ2+ T cells play a critical role in immunity to micro-organisms and cancer but exhibit substantial heterogeneity in humans. Here, we demonstrate that CD26 and CD94 define transcriptionally, phenotypically, and functionally distinct Vδ2+ T cell subsets. Despite distinct antigen specificities, CD26hiCD94lo Vδ2+ cells exhibit substantial similarities to CD26hi mucosal-associated invariant T (MAIT) cells, although CD26− Vδ2+ cells exhibit cytotoxic, effector-like profiles. At birth, the Vδ2+Vγ9+ population is dominated by CD26hiCD94lo cells; during adolescence and adulthood, Vδ2+ cells acquire CD94/NKG2A expression and the relative frequency of the CD26hiCD94lo subset declines. Critically, exposure of the CD26hiCD94lo subset to phosphoantigen in the context of interleukin-23 (IL-23) and CD26 engagement drives the acquisition of a cytotoxic program and concurrent loss of the MAIT cell-like phenotype. The ability to modulate the cytotoxic potential of CD26hiCD94lo Vδ2+ cells, combined with their adenosine-binding capacity, may make them ideal targets for immunotherapeutic expansion and adoptive transfer. Wragg et al. identify a population of human gd T cells with striking similarities to MAIT cells. These cells dominate the cord blood Vd2 population and upregulate an effector-like program upon antigen and IL-23 stimulation, providing a potential mechanism by which cytotoxic Vd2 cells may accumulate during adolescence and adulthood. © 2020
- Description: National Health and Medical Research Council, NHMRC
- Authors: Wragg, Kathleen , Tan, Hyon , Kristensen, Anne , Nguyen-Robertson, Catriona , Kelleher, Anthony , Parsons, Matthew , Wheatley, Adam , Berzins, Stuart , Pellicci, Daniel , Kent, Stephen , Juno, Jennifer
- Date: 2020
- Type: Text , Journal article
- Relation: Cell Reports Vol. 31, no. 11 (2020), p.
- Full Text:
- Reviewed:
- Description: Vδ2+ T cells play a critical role in immunity to micro-organisms and cancer but exhibit substantial heterogeneity in humans. Here, we demonstrate that CD26 and CD94 define transcriptionally, phenotypically, and functionally distinct Vδ2+ T cell subsets. Despite distinct antigen specificities, CD26hiCD94lo Vδ2+ cells exhibit substantial similarities to CD26hi mucosal-associated invariant T (MAIT) cells, although CD26− Vδ2+ cells exhibit cytotoxic, effector-like profiles. At birth, the Vδ2+Vγ9+ population is dominated by CD26hiCD94lo cells; during adolescence and adulthood, Vδ2+ cells acquire CD94/NKG2A expression and the relative frequency of the CD26hiCD94lo subset declines. Critically, exposure of the CD26hiCD94lo subset to phosphoantigen in the context of interleukin-23 (IL-23) and CD26 engagement drives the acquisition of a cytotoxic program and concurrent loss of the MAIT cell-like phenotype. The ability to modulate the cytotoxic potential of CD26hiCD94lo Vδ2+ cells, combined with their adenosine-binding capacity, may make them ideal targets for immunotherapeutic expansion and adoptive transfer. Wragg et al. identify a population of human gd T cells with striking similarities to MAIT cells. These cells dominate the cord blood Vd2 population and upregulate an effector-like program upon antigen and IL-23 stimulation, providing a potential mechanism by which cytotoxic Vd2 cells may accumulate during adolescence and adulthood. © 2020
- Description: National Health and Medical Research Council, NHMRC
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
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- 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
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