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Article ; Online: γδ T Cell Update: Adaptate Orchestrators of Immune Surveillance.

Hayday, Adrian C

Journal of immunology (Baltimore, Md. : 1950)

2019 Volume 203, Issue 2, Page(s) 311–320

Abstract: As interest in γδ T cells grows rapidly, what key points are emerging, and where is caution warranted? γδ T cells fulfill critical functions, as reflected in associations with vaccine responsiveness and cancer survival in humans and ever more phenotypes ... ...

Abstract	As interest in γδ T cells grows rapidly, what key points are emerging, and where is caution warranted? γδ T cells fulfill critical functions, as reflected in associations with vaccine responsiveness and cancer survival in humans and ever more phenotypes of γδ T cell-deficient mice, including basic physiological deficiencies. Such phenotypes reflect activities of distinct γδ T cell subsets, whose origins offer interesting insights into lymphocyte development but whose variable evolutionary conservation can obfuscate translation of knowledge from mice to humans. By contrast, an emerging and conserved feature of γδ T cells is their "adaptate" biology: an integration of adaptive clonally-restricted specificities, innate tissue-sensing, and unconventional recall responses that collectively strengthen host resistance to myriad challenges. Central to adaptate biology are butyrophilins and other γδ cell regulators, the study of which should greatly enhance our understanding of tissue immunogenicity and immunosurveillance and guide intensifying clinical interest in γδ cells and other unconventional lymphocytes.
MeSH term(s)	Animals ; Butyrophilins/immunology ; Humans ; Immunologic Surveillance/immunology ; Monitoring, Immunologic/methods ; Receptors, Antigen, T-Cell, gamma-delta/immunology ; T-Lymphocyte Subsets/immunology
Chemical Substances	Butyrophilins ; Receptors, Antigen, T-Cell, gamma-delta
Language	English
Publishing date	2019-09-04
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; 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.1800934
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Article ; Online: The Innate Biologies of Adaptive Antigen Receptors.

Hayday, Adrian C / Vantourout, Pierre

Annual review of immunology

2020 Volume 38, Page(s) 487–510

Abstract: Nonclonal innate immune responses mediated by germ line-encoded receptors, such as Toll-like receptors or natural killer receptors, are commonly contrasted with diverse, clonotypic adaptive responses of lymphocyte antigen receptors generated by somatic ... ...

Abstract	Nonclonal innate immune responses mediated by germ line-encoded receptors, such as Toll-like receptors or natural killer receptors, are commonly contrasted with diverse, clonotypic adaptive responses of lymphocyte antigen receptors generated by somatic recombination. However, the Variable (V) regions of antigen receptors include germ line-encoded motifs unaltered by somatic recombination, and theoretically available to mediate nonclonal, innate responses, that are independent of or largely override clonotypic responses. Recent evidence demonstrates that such responses exist, underpinning the associations of particular γδ T cell receptors (TCRs) with specific anatomical sites. Thus, TCRγδ can make innate and adaptive responses with distinct functional outcomes. Given that αβ T cells and B cells can also make nonclonal responses, we consider that innate responses of antigen receptor V-regions may be more widespread, for example, inducing states of preparedness from which adaptive clones are better selected. We likewise consider that potent, nonclonal T cell responses to microbial superantigens may reflect subversion of physiologic innate responses of TCRα/β chains.
MeSH term(s)	Adaptive Immunity ; Animals ; Host-Pathogen Interactions/immunology ; Humans ; Immunity, Innate ; Protein Binding ; Protein Interaction Domains and Motifs ; Receptors, Antigen/chemistry ; Receptors, Antigen/genetics ; Receptors, Antigen/metabolism ; Receptors, Antigen, T-Cell/chemistry ; Receptors, Antigen, T-Cell/metabolism ; Signal Transduction
Chemical Substances	Receptors, Antigen ; Receptors, Antigen, T-Cell
Language	English
Publishing date	2020-02-04
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	604953-9
ISSN	1545-3278 ; 0732-0582
ISSN (online)	1545-3278
ISSN	0732-0582
DOI	10.1146/annurev-immunol-102819-023144
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Article ; Online: Corrigendum: To Ki or Not to Ki: Re-Evaluating the Use and Potentials of Ki-67 for T Cell Analysis.

Di Rosa, Francesca / Cossarizza, Andrea / Hayday, Adrian C

Frontiers in immunology

2021 Volume 12, Page(s) 756641

Abstract: This corrects the article DOI: 10.3389/fimmu.2021.653974.]. ...

Abstract	[This corrects the article DOI: 10.3389/fimmu.2021.653974.].
Language	English
Publishing date	2021-09-28
Publishing country	Switzerland
Document type	Published Erratum
ZDB-ID	2606827-8
ISSN	1664-3224 ; 1664-3224
ISSN (online)	1664-3224
ISSN	1664-3224
DOI	10.3389/fimmu.2021.756641
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Article ; Online: To Ki or Not to Ki: Re-Evaluating the Use and Potentials of Ki-67 for T Cell Analysis.

Di Rosa, Francesca / Cossarizza, Andrea / Hayday, Adrian C

Frontiers in immunology

2021 Volume 12, Page(s) 653974

Abstract: This study discusses substantive advances in T cell proliferation analysis, with the aim to provoke a re-evaluation of the generally-held view that Ki-67 is a reliable proliferation ... ...

Abstract	This study discusses substantive advances in T cell proliferation analysis, with the aim to provoke a re-evaluation of the generally-held view that Ki-67 is a reliable proliferation marker
MeSH term(s)	Animals ; CD8-Positive T-Lymphocytes/immunology ; CD8-Positive T-Lymphocytes/pathology ; COVID-19/immunology ; COVID-19/pathology ; COVID-19/prevention & control ; COVID-19 Vaccines/immunology ; COVID-19 Vaccines/therapeutic use ; Cell Cycle/immunology ; Diabetes Mellitus, Type 1/immunology ; Diabetes Mellitus, Type 1/pathology ; Diabetes Mellitus, Type 1/therapy ; Humans ; Ki-67 Antigen/immunology ; Mice ; Neoplasms/immunology ; Neoplasms/pathology ; Neoplasms/therapy ; SARS-CoV-2/immunology
Chemical Substances	COVID-19 Vaccines ; Ki-67 Antigen ; MKI67 protein, human
Language	English
Publishing date	2021-04-09
Publishing country	Switzerland
Document type	Journal Article ; 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.2021.653974
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Article ; Online: Anti-type I interferon antibodies as a cause of severe COVID-19.

Fajgenbaum, David C / Hayday, Adrian C / Rogers, Angela J / Towers, Greg J / Wack, Andreas / Zanoni, Ivan

Faculty reviews

2022 Volume 11, Page(s) 15

Abstract: COVID-19 ranges from asymptomatic through to respiratory failure and death. Although specific pre-existing conditions such as age and male sex have been associated with poor outcomes, we remain largely ignorant of the mechanisms predisposing to severe ... ...

Abstract	COVID-19 ranges from asymptomatic through to respiratory failure and death. Although specific pre-existing conditions such as age and male sex have been associated with poor outcomes, we remain largely ignorant of the mechanisms predisposing to severe disease. In this study, the authors discovered that approximately 10% of 987 patients with life-threatening COVID-19 harbored neutralizing antibodies to Type I interferons (IFNs)
Language	English
Publishing date	2022-06-10
Publishing country	England
Document type	Journal Article ; Comment
ISSN	2732-432X
ISSN (online)	2732-432X
DOI	10.12703/r-01-0000010
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Article ; Online: Durable CD8 T Cell Memory against SARS-CoV-2 by Prime/Boost and Multi-Dose Vaccination: Considerations on Inter-Dose Time Intervals.

Natalini, Ambra / Simonetti, Sonia / Sher, Carmel / D'Oro, Ugo / Hayday, Adrian C / Di Rosa, Francesca

International journal of molecular sciences

2022 Volume 23, Issue 22

Abstract: Facing the COVID-19 pandemic, anti-SARS-CoV-2 vaccines were developed at unprecedented pace, productively exploiting contemporary fundamental research and prior art. Large-scale use of anti-SARS-CoV-2 vaccines has greatly limited severe morbidity and ... ...

Abstract	Facing the COVID-19 pandemic, anti-SARS-CoV-2 vaccines were developed at unprecedented pace, productively exploiting contemporary fundamental research and prior art. Large-scale use of anti-SARS-CoV-2 vaccines has greatly limited severe morbidity and mortality. Protection has been correlated with high serum titres of neutralizing antibodies capable of blocking the interaction between the viral surface protein spike and the host SARS-CoV-2 receptor, ACE-2. Yet, vaccine-induced protection subsides over time, and breakthrough infections are commonly observed, mostly reflecting the decay of neutralizing antibodies and the emergence of variant viruses with mutant spike proteins. Memory CD8 T cells are a potent weapon against viruses, as they are against tumour cells. Anti-SARS-CoV-2 memory CD8 T cells are induced by either natural infection or vaccination and can be potentially exploited against spike-mutated viruses. We offer here an overview of current research about the induction of anti-SARS-CoV-2 memory CD8 T cells by vaccination, in the context of prior knowledge on vaccines and on fundamental mechanisms of immunological memory. We focus particularly on how vaccination by two doses (prime/boost) or more (boosters) promotes differentiation of memory CD8 T cells, and on how the time-length of inter-dose intervals may influence the magnitude and persistence of CD8 T cell memory.
MeSH term(s)	Humans ; SARS-CoV-2 ; Pandemics ; COVID-19/prevention & control ; CD8-Positive T-Lymphocytes ; Vaccination ; Antibodies, Neutralizing
Chemical Substances	Antibodies, Neutralizing
Language	English
Publishing date	2022-11-19
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2019364-6
ISSN	1422-0067 ; 1422-0067 ; 1661-6596
ISSN (online)	1422-0067
ISSN	1422-0067 ; 1661-6596
DOI	10.3390/ijms232214367
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Article ; Online: Normality sensing licenses local T cells for innate-like tissue surveillance.

McKenzie, Duncan R / Hart, Rosie / Bah, Nourdine / Ushakov, Dmitry S / Muñoz-Ruiz, Miguel / Feederle, Regina / Hayday, Adrian C

Nature immunology

2022 Volume 23, Issue 3, Page(s) 411–422

Abstract: The increasing implication of lymphocytes in general physiology and immune surveillance outside of infection poses the question of how their antigen receptors might be involved. Here, we show that macromolecular aggregates of intraepidermal γδ T cell ... ...

Abstract	The increasing implication of lymphocytes in general physiology and immune surveillance outside of infection poses the question of how their antigen receptors might be involved. Here, we show that macromolecular aggregates of intraepidermal γδ T cell antigen receptors (TCRs) in the mouse skin aligned with and depended on Skint1, a butyrophilin-like (BTNL) protein expressed by differentiated keratinocytes (KCs) at steady state. Interruption of TCR-mediated 'normality sensing' had no impact on γδ T cell numbers but altered their signature phenotype, while the epidermal barrier function was compromised. In addition to the regulation of steady-state physiology, normality sensing licensed intraepidermal T cells to respond rapidly to subsequent tissue perturbation by using innate tumor necrosis factor (TNF) superfamily receptors. Thus, interfering with Skint1-dependent interactions between local γδ T cells and KCs at steady state increased the susceptibility to ultraviolet B radiation (UVR)-induced DNA damage and inflammation, two cancer-disposing factors.
MeSH term(s)	Animals ; Butyrophilins ; Epidermis ; Intraepithelial Lymphocytes/metabolism ; Licensure ; Mice ; Receptors, Antigen, T-Cell, gamma-delta/metabolism
Chemical Substances	Butyrophilins ; Receptors, Antigen, T-Cell, gamma-delta
Language	English
Publishing date	2022-02-14
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2016987-5
ISSN	1529-2916 ; 1529-2908
ISSN (online)	1529-2916
ISSN	1529-2908
DOI	10.1038/s41590-021-01124-8
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Article ; Online: Gammadelta T cells and the lymphoid stress-surveillance response.

Hayday, Adrian C

Immunity

2009 Volume 31, Issue 2, Page(s) 184–196

Abstract: The investigation of gammadelta T cells has identified a rapid lymphoid stress-surveillance response to microbial and nonmicrobial tissue perturbation. In addition to providing local protection, this response provides an immediate source of cytokines, ... ...

Abstract	The investigation of gammadelta T cells has identified a rapid lymphoid stress-surveillance response to microbial and nonmicrobial tissue perturbation. In addition to providing local protection, this response provides an immediate source of cytokines, chemokines, and other functions that can substantially affect downstream, adaptive immunity. Recent studies have identified striking mechanisms by which gammadelta cells meet the requirements of stress surveillance. For example, high response frequencies can reflect a unique nature of antigen engagement by the T cell receptor (TCR), developmental focusing of the repertoire by selection events, or the use of nonclonotypic receptors to initiate responses. Likewise, rapid functional deployment can be facilitated by the preprogramming of gammadelta cells during development. Additionally, gammadelta cells can directly influence adaptive immunity by functioning as antigen-presenting cells. With lymphoid stress surveillance likely to underpin numerous aspects of inflammation, tumor immunology, infectious disease, and autoimmunity, this perspective considers its properties and its emerging potential for clinical manipulation.
MeSH term(s)	Animals ; Antigen Presentation/immunology ; Antigens, CD/immunology ; Antigens, CD/metabolism ; Cytokines/immunology ; Cytokines/metabolism ; Humans ; Immunity, Active ; Interleukin-17/immunology ; Interleukin-17/metabolism ; Killer Cells, Natural/immunology ; Killer Cells, Natural/metabolism ; Major Histocompatibility Complex/immunology ; Receptors, Antigen, B-Cell/immunology ; Receptors, Antigen, B-Cell/metabolism ; Receptors, Antigen, T-Cell, gamma-delta/immunology ; Receptors, Antigen, T-Cell, gamma-delta/metabolism ; Stress, Physiological/immunology ; T-Lymphocyte Subsets/immunology ; T-Lymphocyte Subsets/metabolism
Chemical Substances	Antigens, CD ; Cytokines ; Interleukin-17 ; Receptors, Antigen, B-Cell ; Receptors, Antigen, T-Cell, gamma-delta
Language	English
Publishing date	2009-08-20
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	1217235-2
ISSN	1097-4180 ; 1074-7613
ISSN (online)	1097-4180
ISSN	1074-7613
DOI	10.1016/j.immuni.2009.08.006
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Article ; Online: Conserved γδ T cell selection by BTNL proteins limits progression of human inflammatory bowel disease.

Dart, Robin J / Zlatareva, Iva / Vantourout, Pierre / Theodoridis, Efstathios / Amar, Ariella / Kannambath, Shichina / East, Philip / Recaldin, Timothy / Mansfield, John C / Lamb, Christopher A / Parkes, Miles / Irving, Peter M / Prescott, Natalie J / Hayday, Adrian C

Science (New York, N.Y.)

2023 Volume 381, Issue 6663, Page(s) eadh0301

Abstract: Murine intraepithelial γδ T cells include distinct tissue-protective cells selected by epithelial butyrophilin-like (BTNL) heteromers. To determine whether this biology is conserved in humans, we characterized the colonic γδ T cell compartment, ... ...

Abstract	Murine intraepithelial γδ T cells include distinct tissue-protective cells selected by epithelial butyrophilin-like (BTNL) heteromers. To determine whether this biology is conserved in humans, we characterized the colonic γδ T cell compartment, identifying a diverse repertoire that includes a phenotypically distinct subset coexpressing T cell receptor Vγ4 and the epithelium-binding integrin CD103. This subset was disproportionately diminished and dysregulated in inflammatory bowel disease, whereas on-treatment CD103
MeSH term(s)	Animals ; Humans ; Mice ; Butyrophilins/genetics ; Colon/immunology ; Crohn Disease/genetics ; Crohn Disease/immunology ; Inflammatory Bowel Diseases/genetics ; Inflammatory Bowel Diseases/immunology ; Receptors, Antigen, T-Cell, gamma-delta ; T-Lymphocyte Subsets/immunology ; Intestinal Mucosa/immunology
Chemical Substances	Butyrophilins ; Receptors, Antigen, T-Cell, gamma-delta ; alpha E integrins ; BTNL8 protein, human
Language	English
Publishing date	2023-09-15
Publishing country	United States
Document type	Journal Article
ZDB-ID	128410-1
ISSN	1095-9203 ; 0036-8075
ISSN (online)	1095-9203
ISSN	0036-8075
DOI	10.1126/science.adh0301
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Article ; Online: COVID-19: Using high-throughput flow cytometry to dissect clinical heterogeneity.

Del Molino Del Barrio, Irene / Hayday, Thomas S / Laing, Adam G / Hayday, Adrian C / Di Rosa, Francesca

Cytometry. Part A : the journal of the International Society for Analytical Cytology

2021 Volume 103, Issue 2, Page(s) 117–126

Abstract: Here we consider how high-content flow cytometric methodology at appropriate scale and throughput rapidly provided meaningful biological data in our recent studies of COVID-19, which we discuss in the context of other similar investigations. In our work, ...

Abstract	Here we consider how high-content flow cytometric methodology at appropriate scale and throughput rapidly provided meaningful biological data in our recent studies of COVID-19, which we discuss in the context of other similar investigations. In our work, high-throughput flow cytometry was instrumental to identify a consensus immune signature in COVID-19 patients, and to investigate the impact of SARS-CoV-2 exposure on patients with either solid or hematological cancers. We provide here some examples of our 'holistic' approach, in which flow cytometry data generated by lymphocyte and myelomonocyte panels were integrated with other analytical metrics, including SARS-CoV-2-specific serum antibody titers, plasma cytokine/chemokine levels, and in-depth clinical annotation. We report how selective differences between T cell subsets were revealed by a newly described flow cytometric T
MeSH term(s)	Humans ; COVID-19 ; SARS-CoV-2 ; Flow Cytometry ; Cytokines ; T-Lymphocyte Subsets
Chemical Substances	Cytokines
Language	English
Publishing date	2021-11-22
Publishing country	United States
Document type	Journal Article ; Review ; Research Support, Non-U.S. Gov't
ZDB-ID	2099868-5
ISSN	1552-4930 ; 0196-4763 ; 1552-4922
ISSN (online)	1552-4930
ISSN	0196-4763 ; 1552-4922
DOI	10.1002/cyto.a.24516
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