{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T01:29:45Z","timestamp":1787016585313,"version":"build-2736575974"},"reference-count":72,"publisher":"American Association for the Advancement of Science (AAAS)","issue":"765","content-domain":{"domain":["www.science.org"],"crossmark-restriction":true},"short-container-title":["Sci. Transl. Med."],"published-print":{"date-parts":[[2024,9,18]]},"abstract":"<jats:p>\n                    The development of the human immune system lasts for several years after birth. The impact of this maturation phase on the quality of adaptive immunity and the acquisition of immunological memory after infection at a young age remains incompletely defined. Here, using an antigen-reactive T cell (ARTE) assay and multidimensional flow cytometry, we profiled circulating severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)\u2013reactive CD3\n                    <jats:sup>+<\/jats:sup>\n                    CD4\n                    <jats:sup>+<\/jats:sup>\n                    CD154\n                    <jats:sup>+<\/jats:sup>\n                    T cells in children and adults before infection, during infection, and 11 months after infection, stratifying children into separate age groups and adults according to disease severity. During SARS-CoV-2 infection, children younger than 5 years old displayed a lower antiviral CD4\n                    <jats:sup>+<\/jats:sup>\n                    T cell response, whereas children older than 5 years and adults with mild disease had, quantitatively and phenotypically, comparable virus-reactive CD4\n                    <jats:sup>+<\/jats:sup>\n                    T cell responses. Adults with severe disease mounted a response characterized by higher frequencies of virus-reactive proinflammatory and cytotoxic T cells. After SARS-CoV-2 infection, preschool-age children not only maintained neutralizing SARS-CoV-2\u2013reactive antibodies postinfection comparable to adults but also had phenotypically distinct memory T cells displaying high inflammatory features and properties associated with migration toward inflamed sites. Moreover, preschool-age children had markedly fewer circulating virus-reactive memory B cells compared with the other cohorts. Collectively, our results reveal unique facets of antiviral immunity in humans at a young age and indicate that the maturation of adaptive responses against SARS-CoV-2 toward an adult-like profile occurs in a progressive manner.\n                  <\/jats:p>","DOI":"10.1126\/scitranslmed.adl1997","type":"journal-article","created":{"date-parts":[[2024,9,18]],"date-time":"2024-09-18T13:59:01Z","timestamp":1726667941000},"update-policy":"https:\/\/doi.org\/10.34133\/aaas_crossmark","source":"Crossref","is-referenced-by-count":12,"title":["Preschool-age children maintain a distinct memory CD4\n                    <sup>+<\/sup>\n                    T cell and memory B cell response after SARS-CoV-2 infection"],"prefix":"10.1126","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4105-4684","authenticated-orcid":true,"given":"Beno\u00eet","family":"Manfroi","sequence":"first","affiliation":[{"name":"Universit\u00e9 Paris Cit\u00e9, INSERM U1151, CNRS UMR8253, Institut Necker Enfants Malades-INEM, F-75015 Paris, France."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bui Thi","family":"Cuc","sequence":"additional","affiliation":[{"name":"Universit\u00e9 Paris Cit\u00e9, INSERM U1151, CNRS UMR8253, Institut Necker Enfants Malades-INEM, F-75015 Paris, France."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1198-8689","authenticated-orcid":true,"given":"Aur\u00e9lien","family":"Sokal","sequence":"additional","affiliation":[{"name":"Universit\u00e9 Paris Cit\u00e9, INSERM U1151, CNRS UMR8253, Institut Necker Enfants Malades-INEM, F-75015 Paris, France."},{"name":"Action th\u00e9matique incitative sur programme-Avenir Team, Auto-Immune and Immune B cells, F-75015 Paris, France."},{"name":"Service de M\u00e9decine interne, H\u00f4pital Beaujon, Assistance Publique-H\u00f4pitaux de Paris (AP-HP), 92110 Clichy, France."},{"name":"Service de M\u00e9decine Interne, Centre Hospitalier Universitaire Henri-Mondor, Assistance Publique-H\u00f4pitaux de Paris (AP-HP), Universit\u00e9 Paris-Est Cr\u00e9teil (UPEC), 94000 Cr\u00e9teil, France."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexis","family":"Vandenberghe","sequence":"additional","affiliation":[{"name":"Universit\u00e9 Paris Cit\u00e9, INSERM U1151, CNRS UMR8253, Institut Necker Enfants Malades-INEM, F-75015 Paris, France."},{"name":"Action th\u00e9matique incitative sur programme-Avenir Team, Auto-Immune and Immune B cells, F-75015 Paris, France."},{"name":"Service de M\u00e9decine Interne, Centre Hospitalier Universitaire Henri-Mondor, Assistance Publique-H\u00f4pitaux de Paris (AP-HP), Universit\u00e9 Paris-Est Cr\u00e9teil (UPEC), 94000 Cr\u00e9teil, France."},{"name":"INSERM U955, \u00e9quipe 2. Institut Mondor de Recherche Biom\u00e9dicale (IMRB), Universit\u00e9 Paris-Est Cr\u00e9teil (UPEC), 94000 Cr\u00e9teil, France."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3655-9220","authenticated-orcid":true,"given":"Sarah","family":"Temmam","sequence":"additional","affiliation":[{"name":"Pathogen Discovery Laboratory, Institut Pasteur, Universit\u00e9 Paris Cit\u00e9, and Institut Pasteur, the WOAH Collaborating Center for the Detection and Identification in Humans of Emerging Animal Pathogens, Universit\u00e9 Paris Cit\u00e9, 75015 Paris, France."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mika\u00ebl","family":"Attia","sequence":"additional","affiliation":[{"name":"Molecular Genetics of RNA Viruses, Department of Virology, Institut Pasteur, Universit\u00e9 Paris-Cit\u00e9, CNRS UMR 3569, 75015 Paris, France."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2287-2056","authenticated-orcid":true,"given":"Mohamed","family":"El Behi","sequence":"additional","affiliation":[{"name":"Universit\u00e9 Paris Cit\u00e9, INSERM U1151, CNRS UMR8253, Institut Necker Enfants Malades-INEM, F-75015 Paris, France."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4810-2631","authenticated-orcid":true,"given":"Francesco","family":"Camaglia","sequence":"additional","affiliation":[{"name":"Laboratoire de physique de l\u2019\u00c9cole normale sup\u00e9rieure, CNRS, Paris Sciences et Lettres (PSL) University, Sorbonne Universit\u00e9, and Universit\u00e9 de Paris, 75005 Paris, France."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ngan Thu","family":"Nguyen","sequence":"additional","affiliation":[{"name":"Universit\u00e9 Paris Cit\u00e9, INSERM U1151, CNRS UMR8253, Institut Necker Enfants Malades-INEM, F-75015 Paris, France."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7616-164X","authenticated-orcid":true,"given":"Jelka","family":"Pohar","sequence":"additional","affiliation":[{"name":"Universit\u00e9 Paris Cit\u00e9, INSERM U1151, CNRS UMR8253, Institut Necker Enfants Malades-INEM, F-75015 Paris, France."},{"name":"Immunology and Cellular Immunotherapy (ICI) Group, Department of Genetic Toxicology and Cancer Biology, National Institute of Biology, 1000 Ljubljana, Slovenia."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Layale","family":"Salem-Wehbe","sequence":"additional","affiliation":[{"name":"Universit\u00e9 Paris Cit\u00e9, INSERM U1151, CNRS UMR8253, Institut Necker Enfants Malades-INEM, F-75015 Paris, France."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-3001-2096","authenticated-orcid":true,"given":"Valentine","family":"Pottez-Jouatte","sequence":"additional","affiliation":[{"name":"Universit\u00e9 Paris Cit\u00e9, INSERM U1151, CNRS UMR8253, Institut Necker Enfants Malades-INEM, F-75015 Paris, France."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sibyline","family":"Borzakian","sequence":"additional","affiliation":[{"name":"Universit\u00e9 Paris Cit\u00e9, INSERM U1151, CNRS UMR8253, Institut Necker Enfants Malades-INEM, F-75015 Paris, France."},{"name":"CNRS UMR 9187, INSERM U1196, Chemistry and Modeling for the Biological of Cancer, Institut Curie, PSL Research University, 91405 Orsay, France."},{"name":"Universit\u00e9 Paris-Saclay, 91405 Orsay, France."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Narcisse","family":"Elenga","sequence":"additional","affiliation":[{"name":"Service de P\u00e9diatrie, Centre Hospitalier de Cayenne, 97300 French Guiana."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8763-3534","authenticated-orcid":true,"given":"Caroline","family":"Galeotti","sequence":"additional","affiliation":[{"name":"Department of Pediatric Rheumatology, Bic\u00eatre Hospital, AP-HP, Paris-Saclay University, 94275 Le Kremlin-Bic\u00eatre, France."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6511-1674","authenticated-orcid":true,"given":"Guillaume","family":"Morelle","sequence":"additional","affiliation":[{"name":"Department of General Paediatrics, H\u00f4pital Bic\u00eatre, AP-HP, University of Paris Saclay, 94275 Le Kremlin-Bic\u00eatre, France."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-4932-8566","authenticated-orcid":true,"given":"Camille","family":"de truchis de Lays","sequence":"additional","affiliation":[{"name":"Service de P\u00e9diatrie. H\u00f4pital Jean-Verdier, AP-HP, H\u00f4pitaux Universitaires Paris Seine-Saint-Denis, 93140 Bondy, France."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michaela","family":"Semeraro","sequence":"additional","affiliation":[{"name":"University of Paris Cit\u00e9, and Clinical Investigation Center, Clinical Research Unit, Necker-Children\u2019s Hospital, Assistance Publique-H\u00f4pitaux de Paris, 75015 Paris, France."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5666-3012","authenticated-orcid":true,"given":"Anne-Sophie","family":"Romain","sequence":"additional","affiliation":[{"name":"Sorbonne Universit\u00e9, Assistance Publique\u2013H\u00f4pitaux de Paris, Trousseau Hospital, General Paediatrics Department, 75012 Paris, France."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M\u00e9lodie","family":"Aubart","sequence":"additional","affiliation":[{"name":"INSERM U1163, Genetic Predisposition to Infectious Diseases, Imagine Institute, Universit\u00e9 Paris Cit\u00e9, Paris F-75015, France."},{"name":"Pediatric Neurology Department, Necker-Enfants Malades Universitary Hospital, AP-HP, Paris-Cit\u00e9 University, 75015 Paris, France."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Naim","family":"Ouldali","sequence":"additional","affiliation":[{"name":"Department of General Pediatrics, Pediatric Infectious Disease and Internal Medicine, Robert Debr\u00e9 University Hospital, Assistance Publique-H\u00f4pitaux de Paris, 75019 Paris, France."},{"name":"Paris Cit\u00e9 University, INSERM UMR 1137, Infection, Antimicrobials, Modelling, Evolution (IAME), 75018 Paris, France."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3009-252X","authenticated-orcid":true,"given":"Florence","family":"Mahuteau-Betzer","sequence":"additional","affiliation":[{"name":"CNRS UMR 9187, INSERM U1196, Chemistry and Modeling for the Biological of Cancer, Institut Curie, PSL Research University, 91405 Orsay, France."},{"name":"Universit\u00e9 Paris-Saclay, 91405 Orsay, France."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6845-5982","authenticated-orcid":true,"given":"Claire","family":"Beauvineau","sequence":"additional","affiliation":[{"name":"CNRS UMR 9187, INSERM U1196, Chemistry and Modeling for the Biological of Cancer, Institut Curie, PSL Research University, 91405 Orsay, France."},{"name":"Universit\u00e9 Paris-Saclay, 91405 Orsay, France."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elsa","family":"Amouyal","sequence":"additional","affiliation":[{"name":"SIREDO Pediatric Oncology Center, Institut Curie, Paris-Science Lettres University, 75005 Paris, France."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0165-7947","authenticated-orcid":true,"given":"Romain","family":"Berthaud","sequence":"additional","affiliation":[{"name":"Pediatric Nephrology, Maladies R\u00e9nales H\u00e9r\u00e9ditaires de l\u2019Enfant et de l\u2019Adulte (MARHEA) Reference Center, Necker-Children\u2019s Hospital, Assistance Publique-H\u00f4pitaux de Paris, 75015 Paris, France."},{"name":"Necker-Enfants Malades Hospital, Assistance Publique\u2013H\u00f4pitaux de Paris (AP-HP), 75015 Paris, France."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C\u00e9lia","family":"Cr\u00e9tolle","sequence":"additional","affiliation":[{"name":"D\u00e9partement de P\u00e9diatrie, Service de Chirurgie visc\u00e9rale p\u00e9diatrique, H\u00f4pital Universitaire Necker-Enfants Malades, GH Paris Centre, 75015 Paris, France."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marc Duval","family":"Arnould","sequence":"additional","affiliation":[{"name":"Department of General Paediatrics, H\u00f4pital Bic\u00eatre, AP-HP, University of Paris Saclay, 94275 Le Kremlin-Bic\u00eatre, France."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4708-6086","authenticated-orcid":true,"given":"Albert","family":"Faye","sequence":"additional","affiliation":[{"name":"Pediatric Neurology Department, Necker-Enfants Malades Universitary Hospital, AP-HP, Paris-Cit\u00e9 University, 75015 Paris, France."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9919-1243","authenticated-orcid":true,"given":"Mathie","family":"Lorrot","sequence":"additional","affiliation":[{"name":"Sorbonne Universit\u00e9, Assistance Publique\u2013H\u00f4pitaux de Paris, Trousseau Hospital, General Paediatrics Department, 75012 Paris, France."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gr\u00e9goire","family":"Benoist","sequence":"additional","affiliation":[{"name":"Service de p\u00e9diatrie g\u00e9n\u00e9rale et h\u00f4pital de jour allergologie, CHU Ambroise-Par\u00e9, AP-HP, 92100 Boulogne-Billancourt, France."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nelly","family":"Briand","sequence":"additional","affiliation":[{"name":"University of Paris Cit\u00e9, and Clinical Investigation Center, Clinical Research Unit, Necker-Children\u2019s Hospital, Assistance Publique-H\u00f4pitaux de Paris, 75015 Paris, France."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7897-0806","authenticated-orcid":true,"given":"Marie","family":"Courbebaisse","sequence":"additional","affiliation":[{"name":"Facult\u00e9 de M\u00e9decine, Universit\u00e9 Paris Cit\u00e9, 75015 Paris, France."},{"name":"Explorations fonctionnelles r\u00e9nales, Physiologie, H\u00f4pital europ\u00e9en Georges-Pompidou, Assistance Publique-H\u00f4pitaux de Paris, 75908 Paris Cedex 15, France."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0982-1329","authenticated-orcid":true,"given":"Roland","family":"Martin","sequence":"additional","affiliation":[{"name":"Institute of Experimental Immunology, University of Zurich, Winterthurerstrasse 190, 8057 Zurich, Switzerland."},{"name":"Therapeutic Immune Design, Center for Molecular Medicine, Department of Clinical Neuroscience, Karolinska Institute, 171 76 Stockholm, Sweden."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3782-0750","authenticated-orcid":true,"given":"Peter","family":"Van Endert","sequence":"additional","affiliation":[{"name":"Universit\u00e9 Paris Cit\u00e9, INSERM U1151, CNRS UMR8253, Institut Necker Enfants Malades-INEM, F-75015 Paris, France."},{"name":"Service Immunologie Biologique, AP-HP, H\u00f4pital Universitaire Necker-Enfants Malades, F-75015 Paris, France."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5463-6117","authenticated-orcid":true,"given":"Jean-S\u00e9bastien","family":"Hulot","sequence":"additional","affiliation":[{"name":"PARCC, INSERM, Universit\u00e9 Paris Cit\u00e9, 75015 Paris, France."},{"name":"Centre d\u2019Investigation Clinique, AP-HP, INSERM CIC-1418, Europ\u00e9en Georges Pompidou Hospital, 75015 Paris, France."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anne","family":"Blanchard","sequence":"additional","affiliation":[{"name":"Centre d\u2019Investigation Clinique, AP-HP, INSERM CIC-1418, Europ\u00e9en Georges Pompidou Hospital, 75015 Paris, France."},{"name":"Sorbonne Paris Cit\u00e9, Paris Descartes University, 75015 Paris, France."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7323-468X","authenticated-orcid":true,"given":"Eric","family":"Tartour","sequence":"additional","affiliation":[{"name":"Pediatric Nephrology, Maladies R\u00e9nales H\u00e9r\u00e9ditaires de l\u2019Enfant et de l\u2019Adulte (MARHEA) Reference Center, Necker-Children\u2019s Hospital, Assistance Publique-H\u00f4pitaux de Paris, 75015 Paris, France."},{"name":"PARCC, INSERM, Universit\u00e9 Paris Cit\u00e9, 75015 Paris, France."},{"name":"Department of Immunology, H\u00f4pital Europ\u00e9en Georges-Pompidou, AP-HP, CEDEX 15, 75908 Paris, France."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2891-2269","authenticated-orcid":true,"given":"Maria","family":"Leite-de-Moraes","sequence":"additional","affiliation":[{"name":"Universit\u00e9 Paris Cit\u00e9, INSERM U1151, CNRS UMR8253, Institut Necker Enfants Malades-INEM, F-75015 Paris, France."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7742-5523","authenticated-orcid":true,"given":"Guillaume","family":"Lezmi","sequence":"additional","affiliation":[{"name":"Universit\u00e9 Paris Cit\u00e9, INSERM U1151, CNRS UMR8253, Institut Necker Enfants Malades-INEM, F-75015 Paris, France."},{"name":"AP-HP, H\u00f4pital Necker-Enfants Malades, Service de Pneumologie et Allergologie P\u00e9diatriques, 75015 Paris, France."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mickael","family":"M\u00e9nager","sequence":"additional","affiliation":[{"name":"Laboratory of Inflammatory Responses and Transcriptomic Networks in Diseases, Atip-Avenir Team, Universit\u00e9 Paris Cit\u00e9, Imagine Institute, 75015 Paris, France."},{"name":"Labtech Single-Cell@Imagine, Imagine Institute, 75015 Paris, France."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marine","family":"Luka","sequence":"additional","affiliation":[{"name":"Laboratory of Inflammatory Responses and Transcriptomic Networks in Diseases, Atip-Avenir Team, Universit\u00e9 Paris Cit\u00e9, Imagine Institute, 75015 Paris, France."},{"name":"Labtech Single-Cell@Imagine, Imagine Institute, 75015 Paris, France."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4519-4473","authenticated-orcid":true,"given":"Claude-Agn\u00e8s","family":"Reynaud","sequence":"additional","affiliation":[{"name":"Universit\u00e9 Paris Cit\u00e9, INSERM U1151, CNRS UMR8253, Institut Necker Enfants Malades-INEM, F-75015 Paris, France."},{"name":"Action th\u00e9matique incitative sur programme-Avenir Team, Auto-Immune and Immune B cells, F-75015 Paris, France."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8284-0489","authenticated-orcid":true,"given":"Jean-Claude","family":"Weill","sequence":"additional","affiliation":[{"name":"Universit\u00e9 Paris Cit\u00e9, INSERM U1151, CNRS UMR8253, Institut Necker Enfants Malades-INEM, F-75015 Paris, France."},{"name":"Action th\u00e9matique incitative sur programme-Avenir Team, Auto-Immune and Immune B cells, F-75015 Paris, France."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laetitia","family":"Languille","sequence":"additional","affiliation":[{"name":"Service de M\u00e9decine Interne, Centre Hospitalier Universitaire Henri-Mondor, Assistance Publique-H\u00f4pitaux de Paris (AP-HP), Universit\u00e9 Paris-Est Cr\u00e9teil (UPEC), 94000 Cr\u00e9teil, 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