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Article ; Online: Circulating effector γδ T cell populations are associated with acute coronavirus disease 19 in unvaccinated individuals.

von Borstel, Anouk / Nguyen, Thi Ho / Rowntree, Louise C / Ashhurst, Thomas M / Allen, Lilith F / Howson, Lauren J / Holmes, Natasha E / Smibert, Olivia C / Trubiano, Jason A / Gordon, Claire L / Cheng, Allen C / Kent, Stephen J / Rossjohn, Jamie / Kedzierska, Katherine / Davey, Martin S

Immunology and cell biology

2023 Volume 101, Issue 4, Page(s) 321–332

Abstract: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection causes severe coronavirus disease 2019 (COVID-19) in a small proportion of infected individuals. The immune system plays an important role in the defense against SARS-CoV-2, but our ... ...

Abstract	Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection causes severe coronavirus disease 2019 (COVID-19) in a small proportion of infected individuals. The immune system plays an important role in the defense against SARS-CoV-2, but our understanding of the cellular immune parameters that contribute to severe COVID-19 disease is incomplete. Here, we show that populations of effector γδ T cells are associated with COVID-19 in unvaccinated patients with acute disease. We found that circulating CD27
MeSH term(s)	Humans ; T-Lymphocyte Subsets ; Acute Disease ; Receptors, Antigen, T-Cell, gamma-delta ; COVID-19 ; SARS-CoV-2
Chemical Substances	Receptors, Antigen, T-Cell, gamma-delta
Language	English
Publishing date	2023-02-19
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Intramural ; Research Support, Non-U.S. Gov't
ZDB-ID	284057-1
ISSN	1440-1711 ; 0818-9641
ISSN (online)	1440-1711
ISSN	0818-9641
DOI	10.1111/imcb.12623
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Article ; Online: Case Report: Cytomegalovirus Disease Is an Under-Recognized Contributor to Morbidity and Mortality in Common Variable Immunodeficiency.

Chan, Samantha / Godsell, Jack / Horton, Miles / Farchione, Anthony / Howson, Lauren J / Margetts, Mai / Jin, Celina / Chatelier, Josh / Yong, Michelle / Sasadeusz, Joseph / Douglass, Jo A / Slade, Charlotte A / Bryant, Vanessa L

Frontiers in immunology

2022 Volume 13, Page(s) 815193

Abstract: Background: Common Variable Immunodeficiency (CVID) is classified as a 'Predominantly Antibody Deficiency' (PAD), but there is emerging evidence of cellular immunodeficiency in a subset of patients. This evidence includes CVID patients diagnosed with ... ...

Abstract	Background: Common Variable Immunodeficiency (CVID) is classified as a 'Predominantly Antibody Deficiency' (PAD), but there is emerging evidence of cellular immunodeficiency in a subset of patients. This evidence includes CVID patients diagnosed with cytomegalovirus (CMV) infection, a hallmark of 'combined immunodeficiency'. CMV infection also has the potential to drive immune dysregulation contributing to significant morbidity and mortality in CVID. We aim to determine the extent of cellular immune dysfunction in CVID patients, and whether this correlates with CMV infection status. Methods: We conducted a single-center retrospective cohort study of individuals with CVID at the Royal Melbourne Hospital, and identified patients with and without CMV disease or viraemia. We then isolated T-cells from patient and healthy donor blood samples and examined T-cell proliferation and function. Results: Six patients (7.6%, 6/79) had either CMV disease (pneumonitis or gastrointestinal disease), or symptomatic CMV viraemia. A high mortality rate in the cohort of patients with CVID and CMV disease was observed, with 4 deaths in the period of analysis (66.6%, 4/6). Individuals with CMV infection showed reduced T-cell division in response to T-cell receptor (TCR) stimulation when compared with CMV-negative patients. Discussion: This study demonstrates the morbidity and mortality associated with CMV in CVID, and highlights the need for focused interventions for patients with CVID at risk of CMV disease.
MeSH term(s)	Common Variable Immunodeficiency ; Cytomegalovirus ; Cytomegalovirus Infections ; Humans ; Morbidity ; Primary Immunodeficiency Diseases ; Retrospective Studies ; Viremia/complications
Language	English
Publishing date	2022-02-15
Publishing country	Switzerland
Document type	Case Reports ; Research Support, Non-U.S. Gov't
ZDB-ID	2606827-8
ISSN	1664-3224 ; 1664-3224
ISSN (online)	1664-3224
ISSN	1664-3224
DOI	10.3389/fimmu.2022.815193
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Article: MR1-Restricted Mucosal-Associated Invariant T Cells and Their Activation during Infectious Diseases.

Howson, Lauren J / Salio, Mariolina / Cerundolo, Vincenzo

Frontiers in immunology

2015 Volume 6, Page(s) 303

Abstract: MR1-restricted mucosal-associated invariant T (MAIT) cells recognize vitamin B metabolites, which are generated by a broad range of bacteria, from Escherichia coli to Mycobacterium tuberculosis and BCG. MAIT cells have been described as innate sensors of ...

Abstract	MR1-restricted mucosal-associated invariant T (MAIT) cells recognize vitamin B metabolites, which are generated by a broad range of bacteria, from Escherichia coli to Mycobacterium tuberculosis and BCG. MAIT cells have been described as innate sensors of infection as they accumulate early in infected tissues. MAIT cells maintain an activated phenotype throughout the course of infections, secrete inflammatory cytokines, and have the potential to directly kill infected cells, playing an important role in shaping the host response. In this review, we will discuss the current knowledge regarding the molecular mechanisms that underline MAIT cells activation in sterile and non-sterile inflammatory conditions.
Language	English
Publishing date	2015-06-16
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2606827-8
ISSN	1664-3224
ISSN	1664-3224
DOI	10.3389/fimmu.2015.00303
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Article ; Online: Mucosal-Associated Invariant T Cell Effector Function Is an Intrinsic Cell Property That Can Be Augmented by the Metabolic Cofactor α-Ketoglutarate.

Howson, Lauren J / Li, Jasmine / von Borstel, Anouk / Barugahare, Adele / Mak, Jeffrey Y W / Fairlie, David P / McCluskey, James / Turner, Stephen J / Davey, Martin S / Rossjohn, Jamie

Journal of immunology (Baltimore, Md. : 1950)

2021 Volume 206, Issue 7, Page(s) 1425–1435

Abstract: Mucosal-associated invariant T (MAIT) cells are an innate-like population of unconventional T cells that respond rapidly to microbial metabolite Ags or cytokine stimulation. Because of this reactivity and surface expression of ... ...

Abstract	Mucosal-associated invariant T (MAIT) cells are an innate-like population of unconventional T cells that respond rapidly to microbial metabolite Ags or cytokine stimulation. Because of this reactivity and surface expression of CD45RO
MeSH term(s)	Cells, Cultured ; Cytokines/metabolism ; Epigenesis, Genetic ; Humans ; Immunity, Innate ; Jumonji Domain-Containing Histone Demethylases/metabolism ; Ketoglutaric Acids/metabolism ; Lymphocyte Activation ; Mucosal-Associated Invariant T Cells/immunology ; Receptors, Antigen, T-Cell/metabolism
Chemical Substances	Cytokines ; Ketoglutaric Acids ; Receptors, Antigen, T-Cell ; Jumonji Domain-Containing Histone Demethylases (EC 1.14.11.-) ; KDM6B protein, human (EC 1.14.11.-)
Language	English
Publishing date	2021-02-17
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	3056-9
ISSN	1550-6606 ; 0022-1767 ; 1048-3233 ; 1047-7381
ISSN (online)	1550-6606
ISSN	0022-1767 ; 1048-3233 ; 1047-7381
DOI	10.4049/jimmunol.2001048
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Article ; Online: Recognition of the antigen-presenting molecule MR1 by a Vδ3

Rice, Michael T / von Borstel, Anouk / Chevour, Priyanka / Awad, Wael / Howson, Lauren J / Littler, Dene R / Gherardin, Nicholas A / Le Nours, Jérôme / Giles, Edward M / Berry, Richard / Godfrey, Dale I / Davey, Martin S / Rossjohn, Jamie / Gully, Benjamin S

Proceedings of the National Academy of Sciences of the United States of America

2021 Volume 118, Issue 49

Abstract: Unlike conventional αβ T cells, γδ T cells typically recognize nonpeptide ligands independently of major histocompatibility complex (MHC) restriction. Accordingly, the γδ T cell receptor (TCR) can potentially recognize a wide array of ligands; however, ... ...

Abstract	Unlike conventional αβ T cells, γδ T cells typically recognize nonpeptide ligands independently of major histocompatibility complex (MHC) restriction. Accordingly, the γδ T cell receptor (TCR) can potentially recognize a wide array of ligands; however, few ligands have been described to date. While there is a growing appreciation of the molecular bases underpinning variable (V)δ1
MeSH term(s)	Adult ; Antigen Presentation ; Female ; Histocompatibility Antigens Class I/immunology ; Histocompatibility Antigens Class I/metabolism ; Histocompatibility Antigens Class I/physiology ; Humans ; Intraepithelial Lymphocytes/metabolism ; Intraepithelial Lymphocytes/physiology ; Ligands ; Male ; Minor Histocompatibility Antigens/chemistry ; Minor Histocompatibility Antigens/metabolism ; Minor Histocompatibility Antigens/physiology ; Mucosal-Associated Invariant T Cells/immunology ; Receptors, Antigen, T-Cell/immunology ; Receptors, Antigen, T-Cell/metabolism ; Receptors, Antigen, T-Cell/physiology ; Receptors, Antigen, T-Cell, alpha-beta/metabolism ; Receptors, Antigen, T-Cell, gamma-delta/immunology ; Receptors, Antigen, T-Cell, gamma-delta/metabolism ; Receptors, Antigen, T-Cell, gamma-delta/physiology
Chemical Substances	Histocompatibility Antigens Class I ; Ligands ; MR1 protein, human ; Minor Histocompatibility Antigens ; Receptors, Antigen, T-Cell ; Receptors, Antigen, T-Cell, alpha-beta ; Receptors, Antigen, T-Cell, gamma-delta
Language	English
Publishing date	2021-11-22
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	209104-5
ISSN	1091-6490 ; 0027-8424
ISSN (online)	1091-6490
ISSN	0027-8424
DOI	10.1073/pnas.2110288118
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Article ; Online: Venetoclax treatment in patients with cancer has limited impact on circulating T and NK cells.

Teh, Charis E / Peng, Hongke / Luo, Meng-Xiao / Tan, Tania / Trussart, Marie / Howson, Lauren J / Chua, Chong Chyn / Muttiah, Christine / Brown, Fiona / Ritchie, Matthew E / Wei, Andrew H / Roberts, Andrew W / Bryant, Vanessa L / Anderson, Mary Ann / Lindeman, Geoffrey J / Huang, David C S / Thijssen, Rachel / Gray, Daniel H D

Blood advances

2022 Volume 7, Issue 12, Page(s) 2733–2745

Abstract: Venetoclax is an effective treatment for certain blood cancers, such as chronic lymphocytic leukemia (CLL) and acute myeloid leukemia (AML). However, most patients relapse while on venetoclax and further treatment options are limited. Combining ... ...

Abstract	Venetoclax is an effective treatment for certain blood cancers, such as chronic lymphocytic leukemia (CLL) and acute myeloid leukemia (AML). However, most patients relapse while on venetoclax and further treatment options are limited. Combining venetoclax with immunotherapies is an attractive approach; however, a detailed understanding of how venetoclax treatment impacts normal immune cells in patients is lacking. In this study, we performed deep profiling of peripheral blood (PB) cells from patients with CLL and AML before and after short-term treatment with venetoclax using mass cytometry (cytometry by time of flight) and found no impact on the concentrations of key T-cell subsets or their expression of checkpoint molecules. We also analyzed PB from patients with breast cancer receiving venetoclax long-term using a single-cell multiomics approach (cellular indexing of transcriptomes and epitopes by sequencing) and functional assays. We found significant depletion of B-cell populations with low expression of MCL-1 relative to other immune cells, attended by extensive transcriptomic changes. By contrast, there was less impact on circulating T cells and natural killer (NK) cells, with no changes in their subset composition, transcriptome, or function following venetoclax treatment. Our data indicate that venetoclax has minimal impact on circulating T or NK cells, supporting the rationale of combining this BH3 mimetic drug with cancer immunotherapies for more durable antitumor responses.
MeSH term(s)	Humans ; Leukemia, Lymphocytic, Chronic, B-Cell/drug therapy ; Killer Cells, Natural ; Leukemia, Myeloid, Acute/drug therapy ; Bridged Bicyclo Compounds, Heterocyclic/pharmacology ; Bridged Bicyclo Compounds, Heterocyclic/therapeutic use
Chemical Substances	venetoclax (N54AIC43PW) ; Bridged Bicyclo Compounds, Heterocyclic
Language	English
Publishing date	2022-12-14
Publishing country	United States
Document type	Journal Article
ZDB-ID	2915908-8
ISSN	2473-9537 ; 2473-9529
ISSN (online)	2473-9537
ISSN	2473-9529
DOI	10.1182/bloodadvances.2022008221
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Article ; Online: Repeated

von Borstel, Anouk / Chevour, Priyanka / Arsovski, Daniel / Krol, Jelte M M / Howson, Lauren J / Berry, Andrea A / Day, Cheryl L / Ogongo, Paul / Ernst, Joel D / Nomicos, Effie Y H / Boddey, Justin A / Giles, Edward M / Rossjohn, Jamie / Traore, Boubacar / Lyke, Kirsten E / Williamson, Kim C / Crompton, Peter D / Davey, Martin S

Science translational medicine

2021 Volume 13, Issue 622, Page(s) eabe7430

Abstract: ... ...

Abstract	Repeated
MeSH term(s)	Adult ; Australia ; Child ; Humans ; Malaria, Falciparum/parasitology ; Plasmodium falciparum ; Receptors, Antigen, T-Cell, gamma-delta ; T-Lymphocytes
Chemical Substances	Receptors, Antigen, T-Cell, gamma-delta
Language	English
Publishing date	2021-12-01
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, N.I.H., Intramural ; Research Support, Non-U.S. Gov't
ZDB-ID	2518854-9
ISSN	1946-6242 ; 1946-6234
ISSN (online)	1946-6242
ISSN	1946-6234
DOI	10.1126/scitranslmed.abe7430
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Article ; Online: Immunology of a Transmissible Cancer Spreading among Tasmanian Devils.

Woods, Gregory M / Howson, Lauren J / Brown, Gabriella K / Tovar, Cesar / Kreiss, Alexandre / Corcoran, Lynn M / Lyons, A Bruce

Journal of immunology (Baltimore, Md. : 1950)

2015 Volume 195, Issue 1, Page(s) 23–29

Abstract: Devil facial tumor disease (DFTD) is a transmissible cancer that has killed most of the Tasmanian devil (Sarcophilus harrissii) population. Since the first case appeared in the mid-1990s, it has spread relentlessly across the Tasmanian devil's geographic ...

Abstract	Devil facial tumor disease (DFTD) is a transmissible cancer that has killed most of the Tasmanian devil (Sarcophilus harrissii) population. Since the first case appeared in the mid-1990s, it has spread relentlessly across the Tasmanian devil's geographic range. As Tasmanian devils only exist in Tasmania, Australia, DFTD has the potential to cause extinction of this species. The origin of DFTD was a Schwann cell from a female devil. The disease is transmitted when devils bite each other around the facial areas, a behavior synonymous with this species. Every devil that is 'infected' with DFTD dies from the cancer. Once the DFTD cells have been transmitted, they appear to develop into a cancer without inducing an immune response. The DFTD cancer cells avoid allogeneic recognition because they do not express MHC class I molecules on the cell surface. A reduced genetic diversity and the production of immunosuppressive cytokines may also contribute.
MeSH term(s)	Animals ; Bites and Stings/immunology ; Bites and Stings/mortality ; Bites and Stings/pathology ; CD4-Positive T-Lymphocytes/immunology ; CD4-Positive T-Lymphocytes/pathology ; CD8-Positive T-Lymphocytes/immunology ; CD8-Positive T-Lymphocytes/pathology ; Carnivory ; Dendritic Cells/immunology ; Dendritic Cells/pathology ; Disease Transmission, Infectious ; Facial Neoplasms/immunology ; Facial Neoplasms/mortality ; Facial Neoplasms/pathology ; Female ; Histocompatibility Antigens Class I/genetics ; Histocompatibility Antigens Class I/immunology ; Killer Cells, Natural/immunology ; Killer Cells, Natural/pathology ; Male ; Marsupialia/immunology ; Mortality ; Schwann Cells/immunology ; Schwann Cells/pathology ; Tasmania
Chemical Substances	Histocompatibility Antigens Class I
Language	English
Publishing date	2015-07-01
Publishing country	United States
Document type	Journal Article ; Review
ZDB-ID	3056-9
ISSN	1550-6606 ; 0022-1767 ; 1048-3233 ; 1047-7381
ISSN (online)	1550-6606
ISSN	0022-1767 ; 1048-3233 ; 1047-7381
DOI	10.4049/jimmunol.1500131
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Article ; Online: Identification of dendritic cells, B cell and T cell subsets in Tasmanian devil lymphoid tissue; evidence for poor immune cell infiltration into devil facial tumors.

Howson, Lauren J / Morris, Katrina M / Kobayashi, Takumi / Tovar, Cesar / Kreiss, Alexandre / Papenfuss, Anthony T / Corcoran, Lynn / Belov, Katherine / Woods, Gregory M

Anatomical record (Hoboken, N.J. : 2007)

2014 Volume 297, Issue 5, Page(s) 925–938

Abstract: The Tasmanian devil is under threat of extinction due to the transmissible devil facial tumor disease (DFTD). This fatal tumor is an allograft that does not induce an immune response, raising questions about the activity of Tasmanian devil immune cells. ... ...

Abstract	The Tasmanian devil is under threat of extinction due to the transmissible devil facial tumor disease (DFTD). This fatal tumor is an allograft that does not induce an immune response, raising questions about the activity of Tasmanian devil immune cells. T and B cell analysis has been limited by a lack of antibodies, hence the need to produce such reagents. Amino acid sequence analysis revealed that CD4, CD8, IgM, and IgG were closely related to other marsupials. Monoclonal antibodies were produced against CD4, CD8, IgM, and IgG by generating bacterial fusion proteins. These, and commercial antibodies against CD1a and CD83, identified T cells, B cells and dendritic cells by immunohistochemistry. CD4(+) and CD8(+) T cells were identified in pouch young thymus, adult lymph nodes, spleen, bronchus- and gut-associated lymphoid tissue. Their anatomical distribution was characteristic of mammalian lymphoid tissues with more CD4(+) than CD8(+) cells in lymph nodes and splenic white pulp. IgM(+) and IgG(+) B cells were identified in adult lymph nodes, spleen, bronchus-associated lymphoid tissue and gut-associated lymphoid tissue, with more IgM(+) than IgG(+) cells. Dendritic cells were identified in lymph node, spleen and skin. This distribution is consistent with eutherian mammals and other marsupials, indicating they have the immune cell subsets for an anti-tumor immunity. Devil facial tumor disease tumors contained more CD8(+) than CD4(+) cells, but in low numbers. There were also low numbers of CD1a(+) and MHC class II(+) cells, but no CD83(+) IgM(+) or IgG(+) B cells, consistent with poor immune cell infiltration.
MeSH term(s)	Animals ; B-Lymphocytes/immunology ; B-Lymphocytes/pathology ; Dendritic Cells/immunology ; Dendritic Cells/pathology ; Head and Neck Neoplasms/immunology ; Head and Neck Neoplasms/pathology ; Head and Neck Neoplasms/veterinary ; Lymphoid Tissue/immunology ; Lymphoid Tissue/pathology ; Marsupialia/immunology ; T-Lymphocyte Subsets/immunology ; T-Lymphocyte Subsets/pathology
Language	English
Publishing date	2014-03-24
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2269667-2
ISSN	1932-8494 ; 1932-8486
ISSN (online)	1932-8494
ISSN	1932-8486
DOI	10.1002/ar.22904
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Article ; Online: Diverse Streptococcus pneumoniae Strains Drive a Mucosal-Associated Invariant T-Cell Response Through Major Histocompatibility Complex class I-Related Molecule-Dependent and Cytokine-Driven Pathways.

Kurioka, Ayako / van Wilgenburg, Bonnie / Javan, Reza Rezaei / Hoyle, Ryan / van Tonder, Andries J / Harrold, Caroline L / Leng, Tianqi / Howson, Lauren J / Shepherd, Dawn / Cerundolo, Vincenzo / Brueggemann, Angela B / Klenerman, Paul

The Journal of infectious diseases

2017 Volume 217, Issue 6, Page(s) 988–999

Abstract: Mucosal-associated invariant T (MAIT) cells represent an innate T-cell population that can recognize ligands generated by the microbial riboflavin synthesis pathway, presented via the major histocompatibility complex class I-related molecule (MR1). ... ...

Abstract	Mucosal-associated invariant T (MAIT) cells represent an innate T-cell population that can recognize ligands generated by the microbial riboflavin synthesis pathway, presented via the major histocompatibility complex class I-related molecule (MR1). Streptococcus pneumoniae is a major human pathogen that is also associated with commensal carriage; thus, host control at the mucosal interface is critical. The recognition of pneumococci by MAIT cells has not been defined nor have the genomics and transcriptomics of the riboflavin operon. We observed robust recognition of pneumococci by MAIT cells, using both MR1-dependent and MR1-independent pathways. The pathway used was dependent on the antigen-presenting cell. The riboflavin operon was highly conserved across a range of 571 pneumococci from 39 countries, dating back to 1916, and different versions of the riboflavin operon were also identified in related Streptococcus species. These data indicate an important functional relationship between MAIT cells and pneumococci.
MeSH term(s)	Cells, Cultured ; Cytokines/genetics ; Cytokines/metabolism ; Genes, MHC Class I/immunology ; Genome, Bacterial ; Humans ; Immunity, Cellular ; Macrophages ; Mucosal-Associated Invariant T Cells/physiology ; Operon ; Riboflavin/biosynthesis ; Streptococcus pneumoniae/classification ; Streptococcus pneumoniae/genetics ; Up-Regulation
Chemical Substances	Cytokines ; Riboflavin (TLM2976OFR)
Language	English
Publishing date	2017-10-12
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	3019-3
ISSN	1537-6613 ; 0022-1899
ISSN (online)	1537-6613
ISSN	0022-1899
DOI	10.1093/infdis/jix647
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