{"id":26859,"date":"2020-06-11T00:00:31","date_gmt":"2020-06-11T07:00:31","guid":{"rendered":"https:\/\/vermont.salk.edu\/?post_type=disclosure&#038;p=26859"},"modified":"2024-01-30T14:40:54","modified_gmt":"2024-01-30T22:40:54","slug":"how-targeting-killer-t-cells-in-the-lungs-could-lead-to-immunity-against-respiratory-viruses","status":"publish","type":"disclosure","link":"https:\/\/www.salk.edu\/de\/news-release\/how-targeting-killer-t-cells-in-the-lungs-could-lead-to-immunity-against-respiratory-viruses\/","title":{"rendered":"How targeting killer T cells in the lungs could lead to immunity against respiratory viruses"},"content":{"rendered":"<p>LA JOLLA\u2014A significant site of damage during COVID-19 infection is the lungs. Understanding how the lungs\u2019 immune cells are responding to viral infections could help scientists develop a vaccine.<\/p>\n<p>Now, a team of researchers led by Salk Professor <a href=\"https:\/\/www.salk.edu\/de\/scientist\/susan-kaech\/\">Susan Kaech<\/a> has discovered that the cells responsible for long-term immunity in the lungs can be activated more easily than previously thought. The insight, published in the <a href=\"https:\/\/doi.org\/10.1084\/jem.20192291\" target=\"_blank\" rel=\"noopener\"><em>Journal of Experimental Medicine<\/em><\/a> on June 11, 2020, could aid in the development of universal vaccines for influenza and the novel coronavirus.<\/p>\n<div class=\"row\" style=\"\"><div class=\"col-md-12 col-md-push-0\"><div class=\"video-anchor\" id=\"video-olPHgeGsGiQ\"><\/div><div class=\"embed-responsive embed-responsive-16by9\"> <iframe class=\"embed-responsive-item\" src=\"\/\/www.youtube.com\/embed\/olPHgeGsGiQ?rel=0\" webkitallowfullscreen mozallowfullscreen allowfullscreen><\/iframe><\/div><!-- .embed-responsive --><\/div><!-- .col-md-*size --><\/div><!-- .\/row -->\n<p>\u201cInside our lungs exist long-lived killer T cells that recognize specific viruses and protect us against re-infection, should we encounter the virus again. Our results have elucidated the manner by which these cells \u2018see\u2019 the virus upon re-infection and provide rapid immunity,\u201d says Kaech, director of Salk\u2019s NOMIS Center for Immunobiology and Microbial Pathogenesis. \u201cIt also may help us understand long-term immunity as it relates to coronavirus.\u201d<\/p>\n<p>When we are first exposed to bacteria or viruses, such as influenza, one type of our immune cells, known as killer T cells, destroy infected cells to prevent the spread of the disease. Once the pathogen is cleared, these experienced killer T cells (also called killer \u201cmemory\u201d T cells) remain in our body long-term, and \u201cremember\u201d previous invaders. These killer memory T cells enable our immune systems to more rapidly respond to a second attack and effectively provide long-term protective immunity against the invader, a fundamental concept behind vaccination.<\/p>\n<figure id=\"attachment_26863\"  class=\"wp-caption alignright\"><img loading=\"lazy\" decoding=\"async\" width=\"458\" height=\"458\" class=\"img-responsive wp-image-26863 size-col-md-5\" src=\"https:\/\/www.salk.edu\/wp-content\/uploads\/2020\/06\/Kaech-Tcells-458x458.jpg\" alt=\"Lung-specific CD8 killer T cells (blue) in lung tissue (green) surrounded by dendritic lung cells (red).\" srcset=\"https:\/\/www.salk.edu\/wp-content\/uploads\/2020\/06\/Kaech-Tcells-458x458.jpg 458w, https:\/\/www.salk.edu\/wp-content\/uploads\/2020\/06\/Kaech-Tcells-150x150.jpg 150w, https:\/\/www.salk.edu\/wp-content\/uploads\/2020\/06\/Kaech-Tcells-300x300.jpg 300w, https:\/\/www.salk.edu\/wp-content\/uploads\/2020\/06\/Kaech-Tcells-768x768.jpg 768w, https:\/\/www.salk.edu\/wp-content\/uploads\/2020\/06\/Kaech-Tcells-1024x1024.jpg 1024w, https:\/\/www.salk.edu\/wp-content\/uploads\/2020\/06\/Kaech-Tcells-767x767.jpg 767w, https:\/\/www.salk.edu\/wp-content\/uploads\/2020\/06\/Kaech-Tcells-147x147.jpg 147w, https:\/\/www.salk.edu\/wp-content\/uploads\/2020\/06\/Kaech-Tcells-585x585.jpg 585w, https:\/\/www.salk.edu\/wp-content\/uploads\/2020\/06\/Kaech-Tcells-553x553.jpg 553w, https:\/\/www.salk.edu\/wp-content\/uploads\/2020\/06\/Kaech-Tcells-750x750.jpg 750w, https:\/\/www.salk.edu\/wp-content\/uploads\/2020\/06\/Kaech-Tcells-945x945.jpg 945w, https:\/\/www.salk.edu\/wp-content\/uploads\/2020\/06\/Kaech-Tcells-400x400.jpg 400w, https:\/\/www.salk.edu\/wp-content\/uploads\/2020\/06\/Kaech-Tcells-200x200.jpg 200w, https:\/\/www.salk.edu\/wp-content\/uploads\/2020\/06\/Kaech-Tcells.jpg 1080w\" sizes=\"auto, (max-width: 458px) 100vw, 458px\" \/><figcaption class=\"wp-caption-text\">Lung-specific CD8 killer T cells (blue) in lung tissue (green) surrounded by dendritic lung cells (red).<\/p>\n<p><a href=\"https:\/\/www.salk.edu\/wp-content\/uploads\/2020\/06\/Kaech-Tcells.jpg\">Klicken Sie hier<\/a> f\u00fcr ein hochaufl\u00f6sendes Bild.<\/p>\n<p>Kredit: Salk Institut<\/figcaption><\/figure>\n<p>Scientists know a lot about how killer memory T cells get activated in lymphoid organs (such as lymph nodes). Immune messenger cells called dendritic cells present fragments of the virus to the killer memory T cell, similar to a handler presenting a scent to a hound, to license their killer function.<\/p>\n<p>But prior studies had not examined this interaction in vital organs, such as the lung. The lung is a frequent entry site for pathogens such as influenza and coronavirus, so the team set out to confirm whether this long-held dogma applied to killer memory T cells that reside in the lungs.<\/p>\n<p>Kaech and then-graduate student Jun Siong Low, first author of the paper, assumed that dendritic cells would be required to reactivate killer memory T cells to fight a second viral attack. So, they deleted various types of messenger cells one at a time in mice to see if the killer memory T cells would still recognize a second influenza infection. The researchers used a green florescent reporter protein to make the killer memory T cells glow if they recognized the virus. However, each time the researchers deleted a specific cell type, the killer memory T cells in the lungs continued to glow.<\/p>\n<p>\u201cAt first, our results were disappointing because it didn\u2019t seem like our experiments were working; the killer memory T cells in the lungs continued to recognize the virus after the deletion of many different messenger cell types,\u201d says Low, now a postdoctoral fellow at the Institute for Research in Biomedicine (IRB) at the Universit\u00e0 della Svizzera Italiana, in Switzerland. \u201cSoon, we realized that these lung-resident killer memory T cells were special because they were not reliant on any single type of messenger cell. Instead, they could \u2018see\u2019 the second influenza infection through a variety of different messenger cells, including non-immune cells like lung epithelial cells, which was a remarkably exciting finding.\u201d<\/p>\n<figure id=\"attachment_26872\"  class=\"wp-caption alignleft\"><img loading=\"lazy\" decoding=\"async\" width=\"458\" height=\"305\" class=\"img-responsive wp-image-26872 size-col-md-5\" src=\"https:\/\/www.salk.edu\/wp-content\/uploads\/2020\/06\/Susan-Kaech-and-Jun-Siong-Low-458x305.jpg\" alt=\"Susan Kaech and Jun Siong Low\" srcset=\"https:\/\/www.salk.edu\/wp-content\/uploads\/2020\/06\/Susan-Kaech-and-Jun-Siong-Low-458x305.jpg 458w, https:\/\/www.salk.edu\/wp-content\/uploads\/2020\/06\/Susan-Kaech-and-Jun-Siong-Low-300x200.jpg 300w, https:\/\/www.salk.edu\/wp-content\/uploads\/2020\/06\/Susan-Kaech-and-Jun-Siong-Low-768x512.jpg 768w, https:\/\/www.salk.edu\/wp-content\/uploads\/2020\/06\/Susan-Kaech-and-Jun-Siong-Low-1024x683.jpg 1024w, https:\/\/www.salk.edu\/wp-content\/uploads\/2020\/06\/Susan-Kaech-and-Jun-Siong-Low-147x98.jpg 147w, https:\/\/www.salk.edu\/wp-content\/uploads\/2020\/06\/Susan-Kaech-and-Jun-Siong-Low-585x390.jpg 585w, https:\/\/www.salk.edu\/wp-content\/uploads\/2020\/06\/Susan-Kaech-and-Jun-Siong-Low-553x369.jpg 553w, https:\/\/www.salk.edu\/wp-content\/uploads\/2020\/06\/Susan-Kaech-and-Jun-Siong-Low-750x500.jpg 750w, https:\/\/www.salk.edu\/wp-content\/uploads\/2020\/06\/Susan-Kaech-and-Jun-Siong-Low-767x511.jpg 767w, https:\/\/www.salk.edu\/wp-content\/uploads\/2020\/06\/Susan-Kaech-and-Jun-Siong-Low-945x630.jpg 945w, https:\/\/www.salk.edu\/wp-content\/uploads\/2020\/06\/Susan-Kaech-and-Jun-Siong-Low-1250x833.jpg 1250w, https:\/\/www.salk.edu\/wp-content\/uploads\/2020\/06\/Susan-Kaech-and-Jun-Siong-Low-400x267.jpg 400w, https:\/\/www.salk.edu\/wp-content\/uploads\/2020\/06\/Susan-Kaech-and-Jun-Siong-Low.jpg 1500w\" sizes=\"auto, (max-width: 458px) 100vw, 458px\" \/><figcaption class=\"wp-caption-text\">From left: Susan Kaech and Jun Siong Low, wearing a shirt commemorating the 1,846 days he spent conducting his graduate work on viral infections.<\/p>\n<p><a href=\"https:\/\/www.salk.edu\/wp-content\/uploads\/2020\/06\/Susan-Kaech-and-Jun-Siong-Low.jpg\">Klicken Sie hier<\/a> f\u00fcr ein hochaufl\u00f6sendes Bild.<\/p>\n<p>Kredit: Salk Institut<\/figcaption><\/figure>\n<p>In contrast, when the researchers examined the killer memory T cells in the lymph nodes\u2014glands that swell during infections\u2014they found that the killer memory T cells needed dendritic cells to recognize the second viral attack. This suggests that the anatomical location of the killer memory T cells dictates how they get reactivated, challenging the long-held dogma that killer memory T cells require dendritic cells for reactivation. The results help to reshape the paradigm of killer memory T cell activation.<\/p>\n<p>Because lung-resident killer memory T cells can be quickly reactivated by nearly any cell type at the site of pathogen entry, identifying vaccines that can create these lung-resident killer memory T cells will likely be critical for superior immunity to viral infections of the lungs.<\/p>\n<p>\u201cWe will take this knowledge into our next study, where we will examine whether lung-resident killer memory T cells form after a coronavirus infection,\u201d says Kaech, holder of the NOMIS Chair. \u201cSince not all infections induce killer memory T cells, we will determine if these cells form after a coronavirus infection and whether they can be protective against future coronavirus infections.\u201d<\/p>\n<p>Other authors included Yagmur Farsakoglu of Salk; Esen Sefik, Christian C.D. Harman, Ruaidhri Jackson, Justin Shyer, Xiaodong Jiang, and Richard A. Flavell of the Yale University School of Medicine; Maria Carolina Amezcua Vesely of the Universidad Nacional de C\u00f3rdoba, in Argentina; Joseph B. Kelly of Stony Brook University and Linda S. Cauley of the University of Connecticut Health Center.<\/p>\n<p>The work was supported by the NOMIS Foundation; the National Institutes of Health (R01 AI123864, R37 AI066232, S10 OD020142, P30 CA106359-39); A*STAR National Science Scholarship PhD; a Swiss National Science Foundation Early Postdoc Mobility Fellowship (P2BEP3_178444); a George E. Hewitt Foundation fellowship; the Howard Hughes Medical Institute; the Yale Center for Research Computing; the Yale Center for Genome Analysis; and the Waitt Advanced Biophotonics Core at Salk Institute for Biological Studies.<\/p>","protected":false},"featured_media":26863,"template":"","faculty":[311],"disease-research":[122,366],"class_list":["post-26859","disclosure","type-disclosure","status-publish","has-post-thumbnail","hentry","faculty-susan-kaech","disease-research-immune-system-biology","disease-research-infectious-disease"],"acf":[],"yoast_head":"<!-- This site is optimized with the Yoast SEO plugin v27.3 - https:\/\/yoast.com\/product\/yoast-seo-wordpress\/ -->\n<title>How targeting killer T cells in the lungs could lead to immunity against respiratory viruses - Salk Institute for Biological Studies<\/title>\n<meta name=\"robots\" content=\"index, follow, max-snippet:-1, max-image-preview:large, max-video-preview:-1\" \/>\n<link rel=\"canonical\" href=\"https:\/\/www.salk.edu\/de\/news-release\/how-targeting-killer-t-cells-in-the-lungs-could-lead-to-immunity-against-respiratory-viruses\/\" \/>\n<meta property=\"og:locale\" content=\"de_DE\" \/>\n<meta property=\"og:type\" content=\"article\" \/>\n<meta property=\"og:title\" content=\"How targeting killer T cells in the lungs could lead to immunity against respiratory viruses - Salk Institute for Biological Studies\" \/>\n<meta property=\"og:description\" content=\"LA JOLLA\u2014A significant site of damage during COVID-19 infection is the lungs. 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