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  1. Article ; Online: SARS-CoV-2 infection and recovery in children: Distinct T cell responses in MIS-C compared to COVID-19.

    Rybkina, Ksenia / Bell, Joseph N / Bradley, Marissa C / Wohlbold, Teddy / Scafuro, Marika / Meng, Wenzhao / Korenberg, Rebecca C / Davis-Porada, Julia / Anderson, Brett R / Weller, Rachel J / Milner, Joshua D / Moscona, Anne / Porotto, Matteo / Luning Prak, Eline T / Pethe, Kalpana / Connors, Thomas J / Farber, Donna L

    The Journal of experimental medicine

    2023  Volume 220, Issue 8

    Abstract: SARS-CoV-2 infection for most children results in mild or minimal symptoms, though in rare cases severe disease can develop, including a multisystem inflammatory syndrome (MIS-C) with myocarditis. Here, we present longitudinal profiling of immune ... ...

    Abstract SARS-CoV-2 infection for most children results in mild or minimal symptoms, though in rare cases severe disease can develop, including a multisystem inflammatory syndrome (MIS-C) with myocarditis. Here, we present longitudinal profiling of immune responses during acute disease and following recovery in children who developed MIS-C, relative to children who experienced more typical symptoms of COVID-19. T cells in acute MIS-C exhibited transient signatures of activation, inflammation, and tissue residency which correlated with cardiac disease severity, while T cells in acute COVID-19 upregulated markers of follicular helper T cells for promoting antibody production. The resultant memory immune response in recovery showed increased frequencies of virus-specific memory T cells with pro-inflammatory functions in children with prior MIS-C compared to COVID-19 while both cohorts generated comparable antibody responses. Together our results reveal distinct effector and memory T cell responses in pediatric SARS-CoV-2 infection delineated by clinical syndrome, and a potential role for tissue-derived T cells in the immune pathology of systemic disease.
    MeSH term(s) Humans ; Child ; COVID-19 ; SARS-CoV-2 ; Inflammation ; Severity of Illness Index
    Language English
    Publishing date 2023-05-03
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural
    ZDB-ID 218343-2
    ISSN 1540-9538 ; 0022-1007
    ISSN (online) 1540-9538
    ISSN 0022-1007
    DOI 10.1084/jem.20221518
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: Site-specific development and progressive maturation of human tissue-resident memory T cells over infancy and childhood.

    Connors, Thomas J / Matsumoto, Rei / Verma, Shivali / Szabo, Peter A / Guyer, Rebecca / Gray, Joshua / Wang, Zicheng / Thapa, Puspa / Dogra, Pranay / Poon, Maya M L / Rybkina, Ksenia / Bradley, Marissa C / Idzikowski, Emma / McNichols, James / Kubota, Masaru / Pethe, Kalpana / Shen, Yufeng / Atkinson, Mark A / Brusko, Maigan /
    Brusko, Todd M / Yates, Andrew J / Sims, Peter A / Farber, Donna L

    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
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: Induction of bronchus-associated lymphoid tissue is an early life adaptation for promoting human B cell immunity.

    Matsumoto, Rei / Gray, Joshua / Rybkina, Ksenia / Oppenheimer, Hanna / Levy, Lior / Friedman, Lilach M / Khamaisi, Muhammad / Meng, Wenzhao / Rosenfeld, Aaron M / Guyer, Rebecca S / Bradley, Marissa C / Chen, David / Atkinson, Mark A / Brusko, Todd M / Brusko, Maigan / Connors, Thomas J / Luning Prak, Eline T / Hershberg, Uri / Sims, Peter A /
    Hertz, Tomer / Farber, Donna L

    Nature immunology

    2023  Volume 24, Issue 8, Page(s) 1370–1381

    Abstract: Infants and young children are more susceptible to common respiratory pathogens than adults but can fare better against novel pathogens like severe acute respiratory syndrome coronavirus 2. The mechanisms by which infants and young children mount ... ...

    Abstract Infants and young children are more susceptible to common respiratory pathogens than adults but can fare better against novel pathogens like severe acute respiratory syndrome coronavirus 2. The mechanisms by which infants and young children mount effective immune responses to respiratory pathogens are unknown. Through investigation of lungs and lung-associated lymph nodes from infant and pediatric organ donors aged 0-13 years, we show that bronchus-associated lymphoid tissue (BALT), containing B cell follicles, CD4
    MeSH term(s) Adult ; Infant ; Humans ; Child ; Child, Preschool ; Lymphoid Tissue ; Bronchi/pathology ; COVID-19/pathology ; B-Lymphocytes ; Lymph Nodes
    Language English
    Publishing date 2023-07-17
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural ; 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/s41590-023-01557-3
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    Zs.MG 42: Show issues

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  4. Article ; Online: SARS-CoV-2 infection generates tissue-localized immunological memory in humans.

    Poon, Maya M L / Rybkina, Ksenia / Kato, Yu / Kubota, Masaru / Matsumoto, Rei / Bloom, Nathaniel I / Zhang, Zeli / Hastie, Kathryn M / Grifoni, Alba / Weiskopf, Daniela / Wells, Steven B / Ural, Basak B / Lam, Nora / Szabo, Peter A / Dogra, Pranay / Lee, Yoon S / Gray, Joshua I / Bradley, Marissa C / Brusko, Maigan A /
    Brusko, Todd M / Saphire, Erica O / Connors, Thomas J / Sette, Alessandro / Crotty, Shane / Farber, Donna L

    Science immunology

    2021  Volume 6, Issue 65, Page(s) eabl9105

    Abstract: Adaptive immune responses to SARS-CoV-2 infection have been extensively characterized in blood; however, most functions of protective immunity must be accomplished in tissues. Here, we report from examination of SARS-CoV-2 seropositive organ donors (ages ...

    Abstract Adaptive immune responses to SARS-CoV-2 infection have been extensively characterized in blood; however, most functions of protective immunity must be accomplished in tissues. Here, we report from examination of SARS-CoV-2 seropositive organ donors (ages 10 to 74) that CD4
    MeSH term(s) Antibodies, Viral/immunology ; COVID-19/immunology ; Female ; Humans ; Immunity, Cellular ; Immunologic Memory ; Lymphocytes/immunology ; Male ; Organ Specificity/immunology ; SARS-CoV-2/immunology
    Chemical Substances Antibodies, Viral
    Language English
    Publishing date 2021-11-19
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't, Non-P.H.S.
    ISSN 2470-9468
    ISSN (online) 2470-9468
    DOI 10.1126/sciimmunol.abl9105
    Database MEDical Literature Analysis and Retrieval System OnLINE

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