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Article ; Online: Lasting memories of SARS-CoV-2 infection.

Poon, Maya M L / Farber, Donna L

2021 Volume 218, Issue 4

Abstract: Maintaining virus-specific adaptive immunity is critical for ongoing protection against SARS-CoV-2 infection. In this issue, Breton et al. (2021. J. Exp. Med.https://doi.org/10.1084/jem.20202515) identify polyfunctional SARS-CoV-2-specific T cell ... ...

Abstract	Maintaining virus-specific adaptive immunity is critical for ongoing protection against SARS-CoV-2 infection. In this issue, Breton et al. (2021. J. Exp. Med.https://doi.org/10.1084/jem.20202515) identify polyfunctional SARS-CoV-2-specific T cell responses in the peripheral blood of individuals who recovered from COVID-19 that were present at 1 mo and persisted until 6 mo after infection.
MeSH term(s)	COVID-19 ; Humans ; Immunity, Cellular ; SARS-CoV-2 ; T-Lymphocytes
Language	English
Publishing date	2021-03-18
Publishing country	United States
Document type	Journal Article ; Comment
ZDB-ID	218343-2
ISSN	1540-9538 ; 0022-1007
ISSN (online)	1540-9538
ISSN	0022-1007
DOI	10.1084/jem.20210210
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Zs.MG 45: Show issues

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Article ; Online: The Whole Body as the System in Systems Immunology.

Poon, Maya M L / Farber, Donna L

iScience

2020 Volume 23, Issue 9, Page(s) 101509

Abstract: The human immune system is comprised of a diverse and interactive network of specialized cells localized in diverse tissues throughout the body, where they mediate protection against pathogens and environmental insults while maintaining tissue ... ...

Abstract	The human immune system is comprised of a diverse and interactive network of specialized cells localized in diverse tissues throughout the body, where they mediate protection against pathogens and environmental insults while maintaining tissue homeostasis. Although much of our understanding of human immunology has derived from studies of peripheral blood, recent work utilizing human tissue resources and innovative computational methods have employed a whole-body, systems-based approach, revealing tremendous complexity and heterogeneity of the immune system within individuals and across the population. In this review, we discuss how tissue localization, developmental and age-associated changes, and conditions of health and disease shape the immune response, as well as how improved understanding of interindividual and tissue-specific immunity can be leveraged for developing targeted therapeutics.
Language	English
Publishing date	2020-08-28
Publishing country	United States
Document type	Journal Article ; Review
ISSN	2589-0042
ISSN (online)	2589-0042
DOI	10.1016/j.isci.2020.101509
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Article ; Online: The Whole Body as the System in Systems Immunology

Maya M.L. Poon / Donna L. Farber

iScience, Vol 23, Iss 9, Pp 101509- (2020)

2020

Abstract: Summary: The human immune system is comprised of a diverse and interactive network of specialized cells localized in diverse tissues throughout the body, where they mediate protection against pathogens and environmental insults while maintaining tissue ... ...

Abstract	Summary: The human immune system is comprised of a diverse and interactive network of specialized cells localized in diverse tissues throughout the body, where they mediate protection against pathogens and environmental insults while maintaining tissue homeostasis. Although much of our understanding of human immunology has derived from studies of peripheral blood, recent work utilizing human tissue resources and innovative computational methods have employed a whole-body, systems-based approach, revealing tremendous complexity and heterogeneity of the immune system within individuals and across the population. In this review, we discuss how tissue localization, developmental and age-associated changes, and conditions of health and disease shape the immune response, as well as how improved understanding of interindividual and tissue-specific immunity can be leveraged for developing targeted therapeutics.
Keywords	Immunology ; Complex System Biology ; Science ; Q
Language	English
Publishing date	2020-09-01T00:00:00Z
Publisher	Elsevier
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Tissue adaptation and clonal segregation of human memory T cells in barrier sites.

Poon, Maya M L / Caron, Daniel P / Wang, Zicheng / Wells, Steven B / Chen, David / Meng, Wenzhao / Szabo, Peter A / Lam, Nora / Kubota, Masaru / Matsumoto, Rei / Rahman, Adeeb / Luning Prak, Eline T / Shen, Yufeng / Sims, Peter A / Farber, Donna L

Nature immunology

2023 Volume 24, Issue 2, Page(s) 309–319

Abstract: T lymphocytes migrate to barrier sites after exposure to pathogens, providing localized immunity and long-term protection. Here, we obtained blood and tissues from human organ donors to examine T cells across major barrier sites (skin, lung, jejunum), ... ...

Abstract	T lymphocytes migrate to barrier sites after exposure to pathogens, providing localized immunity and long-term protection. Here, we obtained blood and tissues from human organ donors to examine T cells across major barrier sites (skin, lung, jejunum), associated lymph nodes, lymphoid organs (spleen, bone marrow), and in circulation. By integrating single-cell protein and transcriptome profiling, we demonstrate that human barrier sites contain tissue-resident memory T (T
MeSH term(s)	Humans ; Memory T Cells ; Immunologic Memory ; Lymph Nodes ; Clone Cells ; Cell Differentiation ; CD8-Positive T-Lymphocytes
Language	English
Publishing date	2023-01-19
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, U.S. Gov't, Non-P.H.S.
ZDB-ID	2016987-5
ISSN	1529-2916 ; 1529-2908
ISSN (online)	1529-2916
ISSN	1529-2908
DOI	10.1038/s41590-022-01395-9
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Zs.A 5294: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (2.OG) ab Jg. 2022: Lesesaal (EG)
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Article ; Online: Inhaled particulate accumulation with age impairs immune function and architecture in human lung lymph nodes.

Ural, Basak B / Caron, Daniel P / Dogra, Pranay / Wells, Steven B / Szabo, Peter A / Granot, Tomer / Senda, Takashi / Poon, Maya M L / Lam, Nora / Thapa, Puspa / Lee, Yoon Seung / Kubota, Masaru / Matsumoto, Rei / Farber, Donna L

Nature medicine

2022 Volume 28, Issue 12, Page(s) 2622–2632

Abstract: Older people are particularly susceptible to infectious and neoplastic diseases of the lung and it is unclear how lifelong exposure to environmental pollutants affects respiratory immune function. In an analysis of human lymph nodes (LNs) from 84 organ ... ...

Abstract	Older people are particularly susceptible to infectious and neoplastic diseases of the lung and it is unclear how lifelong exposure to environmental pollutants affects respiratory immune function. In an analysis of human lymph nodes (LNs) from 84 organ donors aged 11-93 years, we found a specific age-related decline in lung-associated, but not gut-associated, LN immune function linked to the accumulation of inhaled atmospheric particulate matter. Increasing densities of particulates were found in lung-associated LNs with age, but not in the corresponding gut-associated LNs. Particulates were specifically contained within CD68
MeSH term(s)	Humans ; Aged ; Lymph Nodes/pathology ; Lung ; Disease Susceptibility/pathology ; Dust ; Immunity
Chemical Substances	Dust
Language	English
Publishing date	2022-11-21
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't, Non-P.H.S. ; Research Support, N.I.H., Extramural
ZDB-ID	1220066-9
ISSN	1546-170X ; 1078-8956
ISSN (online)	1546-170X
ISSN	1078-8956
DOI	10.1038/s41591-022-02073-x
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Zs.A 4212: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (2.OG) ab Jg. 2022: Lesesaal (EG)
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Article ; Online: Site-specific development and progressive maturation of human tissue-resident memory T cells over infancy and childhood.

Immunity

2023 Volume 56, Issue 8, Page(s) 1894–1909.e5

Abstract: Infancy and childhood are critical life stages for generating immune memory to protect against pathogens; however, the timing, location, and pathways for memory development in humans remain elusive. Here, we investigated T cells in mucosal sites, ... ...

Abstract	Infancy and childhood are critical life stages for generating immune memory to protect against pathogens; however, the timing, location, and pathways for memory development in humans remain elusive. Here, we investigated T cells in mucosal sites, lymphoid tissues, and blood from 96 pediatric donors aged 0-10 years using phenotypic, functional, and transcriptomic profiling. Our results revealed that memory T cells preferentially localized in the intestines and lungs during infancy and accumulated more rapidly in mucosal sites compared with blood and lymphoid organs, consistent with site-specific antigen exposure. Early life mucosal memory T cells exhibit distinct functional capacities and stem-like transcriptional profiles. In later childhood, they progressively adopt proinflammatory functions and tissue-resident signatures, coincident with increased T cell receptor (TCR) clonal expansion in mucosal and lymphoid sites. Together, our findings identify staged development of memory T cells targeted to tissues during the formative years, informing how we might promote and monitor immunity in children.
MeSH term(s)	Child ; Humans ; Infant ; CD8-Positive T-Lymphocytes ; Immunologic Memory ; Lymphoid Tissue/metabolism ; Memory T Cells ; Mucous Membrane ; Receptors, Antigen, T-Cell/genetics ; Receptors, Antigen, T-Cell/metabolism ; Infant, Newborn ; Child, Preschool
Chemical Substances	Receptors, Antigen, T-Cell
Language	English
Publishing date	2023-07-07
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; 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.2023.06.008
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Zs.A 4227: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (2.OG) ab Jg. 2022: Lesesaal (EG)
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Article ; Online: Maintenance of the human memory T cell repertoire by subset and tissue site.

Miron, Michelle / Meng, Wenzhao / Rosenfeld, Aaron M / Dvorkin, Shirit / Poon, Maya Meimei Li / Lam, Nora / Kumar, Brahma V / Louzoun, Yoram / Luning Prak, Eline T / Farber, Donna L

Genome medicine

2021 Volume 13, Issue 1, Page(s) 100

Abstract: Background: Immune-mediated protection is mediated by T cells expressing pathogen-specific T cell antigen receptors (TCR) that are maintained at diverse sites of infection as tissue-resident memory T cells (TRM) or that disseminate as circulating ... ...

Abstract	Background: Immune-mediated protection is mediated by T cells expressing pathogen-specific T cell antigen receptors (TCR) that are maintained at diverse sites of infection as tissue-resident memory T cells (TRM) or that disseminate as circulating effector-memory (TEM), central memory (TCM), or terminal effector (TEMRA) subsets in blood and tissues. The relationship between circulating and tissue resident T cell subsets in humans remains elusive, and is important for promoting site-specific protective immunity. Methods: We analyzed the TCR repertoire of the major memory CD4 Results: Across blood, lymphoid organs, and lungs, human memory, and effector CD8 Conclusions: Our results show that the human memory T cell repertoire comprises clones which persist across sites and subsets, along with clones that are more restricted to certain subsets and/or tissue sites. We also provide evidence that the tissue plays a key role in maintaining memory T cells over age, bolstering the rationale for site-specific targeting of memory reservoirs in vaccines and immunotherapies.
MeSH term(s)	Adult ; Age Factors ; Aged ; Aged, 80 and over ; Cell Lineage/genetics ; Clonal Evolution/genetics ; Computational Biology/methods ; Female ; Genetic Variation ; Humans ; Immunity ; Immunogenetic Phenomena ; Immunologic Memory ; Leukocytes, Mononuclear/immunology ; Leukocytes, Mononuclear/metabolism ; Lymphocyte Activation/immunology ; Male ; Memory T Cells/immunology ; Memory T Cells/metabolism ; Middle Aged ; Models, Biological ; Organ Specificity/immunology ; Receptors, Antigen, T-Cell/genetics ; Receptors, Antigen, T-Cell/metabolism ; T-Lymphocyte Subsets/immunology ; T-Lymphocyte Subsets/metabolism
Chemical Substances	Receptors, Antigen, T-Cell
Language	English
Publishing date	2021-06-14
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	2484394-5
ISSN	1756-994X ; 1756-994X
ISSN (online)	1756-994X
ISSN	1756-994X
DOI	10.1186/s13073-021-00918-7
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Article ; Online: Immune and epithelial determinants of age-related risk and alveolar injury in fatal COVID-19.

Chait, Michael / Yilmaz, Mine M / Shakil, Shanila / Ku, Amy W / Dogra, Pranay / Connors, Thomas J / Szabo, Peter A / Gray, Joshua I / Wells, Steven B / Kubota, Masaru / Matsumoto, Rei / Poon, Maya Ml / Snyder, Mark E / Baldwin, Matthew R / Sims, Peter A / Saqi, Anjali / Farber, Donna L / Weisberg, Stuart P

JCI insight

2022 Volume 7, Issue 11

Abstract: Respiratory failure in COVID-19 is characterized by widespread disruption of the lung's alveolar gas exchange interface. To elucidate determinants of alveolar lung damage, we performed epithelial and immune cell profiling in lungs from 24 COVID-19 ... ...

Abstract	Respiratory failure in COVID-19 is characterized by widespread disruption of the lung's alveolar gas exchange interface. To elucidate determinants of alveolar lung damage, we performed epithelial and immune cell profiling in lungs from 24 COVID-19 autopsies and 43 uninfected organ donors ages 18-92 years. We found marked loss of type 2 alveolar epithelial (T2AE) cells and increased perialveolar lymphocyte cytotoxicity in all fatal COVID-19 cases, even at early stages before typical patterns of acute lung injury are histologically apparent. In lungs from uninfected organ donors, there was also progressive loss of T2AE cells with increasing age, which may increase susceptibility to COVID-19-mediated lung damage in older individuals. In the fatal COVID-19 cases, macrophage infiltration differed according to the histopathological pattern of lung injury. In cases with acute lung injury, we found accumulation of CD4+ macrophages that expressed distinctly high levels of T cell activation and costimulation genes and strongly correlated with increased extent of alveolar epithelial cell depletion and CD8+ T cell cytotoxicity. Together, our results show that T2AE cell deficiency may underlie age-related COVID-19 risk and initiate alveolar dysfunction shortly after infection, and we define immune cell mediators that may contribute to alveolar injury in distinct pathological stages of fatal COVID-19.
MeSH term(s)	Acute Lung Injury/pathology ; Adolescent ; Adult ; Aged ; Aged, 80 and over ; Alveolar Epithelial Cells/pathology ; Autopsy ; COVID-19 ; Humans ; Lung/pathology ; Middle Aged ; Young Adult
Language	English
Publishing date	2022-06-08
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, N.I.H., Extramural
ISSN	2379-3708
ISSN (online)	2379-3708
DOI	10.1172/jci.insight.157608
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Article ; Online: Immune and epithelial determinants of age-related risk and alveolar injury in fatal COVID-19

Michael Chait / Mine M. Yilmaz / Shanila Shakil / Amy W. Ku / Pranay Dogra / Thomas J. Connors / Peter A. Szabo / Joshua I. Gray / Steven B. Wells / Masaru Kubota / Rei Matsumoto / Maya M.L. Poon / Mark E. Snyder / Matthew R. Baldwin / Peter A. Sims / Anjali Saqi / Donna L. Farber / Stuart P. Weisberg

JCI Insight, Vol 7, Iss

2022 Volume 11

Abstract: Respiratory failure in COVID-19 is characterized by widespread disruption of the lung’s alveolar gas exchange interface. To elucidate determinants of alveolar lung damage, we performed epithelial and immune cell profiling in lungs from 24 COVID-19 ... ...

Abstract	Respiratory failure in COVID-19 is characterized by widespread disruption of the lung’s alveolar gas exchange interface. To elucidate determinants of alveolar lung damage, we performed epithelial and immune cell profiling in lungs from 24 COVID-19 autopsies and 43 uninfected organ donors ages 18–92 years. We found marked loss of type 2 alveolar epithelial (T2AE) cells and increased perialveolar lymphocyte cytotoxicity in all fatal COVID-19 cases, even at early stages before typical patterns of acute lung injury are histologically apparent. In lungs from uninfected organ donors, there was also progressive loss of T2AE cells with increasing age, which may increase susceptibility to COVID-19–mediated lung damage in older individuals. In the fatal COVID-19 cases, macrophage infiltration differed according to the histopathological pattern of lung injury. In cases with acute lung injury, we found accumulation of CD4+ macrophages that expressed distinctly high levels of T cell activation and costimulation genes and strongly correlated with increased extent of alveolar epithelial cell depletion and CD8+ T cell cytotoxicity. Together, our results show that T2AE cell deficiency may underlie age-related COVID-19 risk and initiate alveolar dysfunction shortly after infection, and we define immune cell mediators that may contribute to alveolar injury in distinct pathological stages of fatal COVID-19.
Keywords	Aging ; COVID-19 ; Medicine ; R
Subject code	610
Language	English
Publishing date	2022-06-01T00:00:00Z
Publisher	American Society for Clinical investigation
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Maintenance of the human memory T cell repertoire by subset and tissue site

Michelle Miron / Wenzhao Meng / Aaron M. Rosenfeld / Shirit Dvorkin / Maya Meimei Li Poon / Nora Lam / Brahma V. Kumar / Yoram Louzoun / Eline T. Luning Prak / Donna L. Farber

Genome Medicine, Vol 13, Iss 1, Pp 1-

2021 Volume 14

Abstract: Abstract Background Immune-mediated protection is mediated by T cells expressing pathogen-specific T cell antigen receptors (TCR) that are maintained at diverse sites of infection as tissue-resident memory T cells (TRM) or that disseminate as circulating ...

Abstract	Abstract Background Immune-mediated protection is mediated by T cells expressing pathogen-specific T cell antigen receptors (TCR) that are maintained at diverse sites of infection as tissue-resident memory T cells (TRM) or that disseminate as circulating effector-memory (TEM), central memory (TCM), or terminal effector (TEMRA) subsets in blood and tissues. The relationship between circulating and tissue resident T cell subsets in humans remains elusive, and is important for promoting site-specific protective immunity. Methods We analyzed the TCR repertoire of the major memory CD4+ and CD8+T cell subsets (TEM, TCM, TEMRA, and TRM) isolated from blood and/or lymphoid organs (spleen, lymph nodes, bone marrow) and lungs of nine organ donors, and blood of three living individuals spanning five decades of life. High-throughput sequencing of the variable (V) portion of individual TCR genes for each subset, tissue, and individual were analyzed for clonal diversity, expansion and overlap between lineage, T cell subsets, and anatomic sites. TCR repertoires were further analyzed for TRBV gene usage and CDR3 edit distance. Results Across blood, lymphoid organs, and lungs, human memory, and effector CD8+T cells exhibit greater clonal expansion and distinct TRBV usage compared to CD4+T cell subsets. Extensive sharing of clones between tissues was observed for CD8+T cells; large clones specific to TEMRA cells were present in all sites, while TEM cells contained clones shared between sites and with TRM. For CD4+T cells, TEM clones exhibited the most sharing between sites, followed by TRM, while TCM clones were diverse with minimal sharing between sites and subsets. Within sites, TRM clones exhibited tissue-specific expansions, and maintained clonal diversity with age, compared to age-associated clonal expansions in circulating memory subsets. Edit distance analysis revealed tissue-specific biases in clonal similarity. Conclusions Our results show that the human memory T cell repertoire comprises clones which persist across ...
Keywords	Immunogenomics ; Immunology ; T cell ; Immunity ; Medicine ; R ; Genetics ; QH426-470
Subject code	612
Language	English
Publishing date	2021-06-01T00:00:00Z
Publisher	BMC
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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