γδ T cell profiling in a cohort of preterm infants reveals elevated frequencies of CD83+ γδ T cells in sepsis
Preterm infants are at high risk of developing neonatal sepsis. γδ T cells are thought to be an important set of effector cells in neonates. Here, γδ T cells were investigated in a longitudinal cohort of preterm neonates using next-generation sequencing, flow cytometry, and functional assays. During...
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| Veröffentlicht in: | The Journal of experimental medicine 2024-07, Vol.221 (7) |
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| creator | León-Lara, Ximena Fichtner, Alina S Willers, Maike Yang, Tao Schaper, Katharina Riemann, Lennart Schöning, Jennifer Harms, Anna Almeida, Vicente Schimrock, Anja Janssen, Anika Ospina-Quintero, Laura von Kaisenberg, Constantin Förster, Reinhold Eberl, Matthias Richter, Manuela F Pirr, Sabine Viemann, Dorothee Ravens, Sarina |
| description | Preterm infants are at high risk of developing neonatal sepsis. γδ T cells are thought to be an important set of effector cells in neonates. Here, γδ T cells were investigated in a longitudinal cohort of preterm neonates using next-generation sequencing, flow cytometry, and functional assays. During the first year of life, the Vγ9Vδ2 T cell subset showed dynamic phenotypic changes and elevated levels of fetal-derived Vγ9Vδ2 T cells were evident in infants with sepsis. Single-cell transcriptomics identified HLA-DRhiCD83+ γδ T cells in neonatal sepsis, which expressed genes related to antigen presentation. In vitro assays showed that CD83 was expressed on activated Vγ9Vδ2 T cells in preterm and term neonates, but not in adults. In contrast, activation of adult Vγ9Vδ2 T cells enhanced CD86 expression, which was presumably the key receptor to induce CD4 T cell proliferation. Together, we provide a map of the maturation of γδ T cells after preterm birth and highlight their phenotypic diversity in infections. |
| doi_str_mv | 10.1084/jem.20231987 |
| format | Article |
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Here, γδ T cells were investigated in a longitudinal cohort of preterm neonates using next-generation sequencing, flow cytometry, and functional assays. During the first year of life, the Vγ9Vδ2 T cell subset showed dynamic phenotypic changes and elevated levels of fetal-derived Vγ9Vδ2 T cells were evident in infants with sepsis. Single-cell transcriptomics identified HLA-DRhiCD83+ γδ T cells in neonatal sepsis, which expressed genes related to antigen presentation. In vitro assays showed that CD83 was expressed on activated Vγ9Vδ2 T cells in preterm and term neonates, but not in adults. In contrast, activation of adult Vγ9Vδ2 T cells enhanced CD86 expression, which was presumably the key receptor to induce CD4 T cell proliferation. Together, we provide a map of the maturation of γδ T cells after preterm birth and highlight their phenotypic diversity in infections.</description><identifier>ISSN: 0022-1007</identifier><identifier>ISSN: 1540-9538</identifier><identifier>EISSN: 1540-9538</identifier><identifier>DOI: 10.1084/jem.20231987</identifier><identifier>PMID: 38753245</identifier><language>eng</language><publisher>United States: Rockefeller University Press</publisher><subject>Adult ; Antigens, CD - genetics ; Antigens, CD - metabolism ; CD83 Antigen ; Cohort Studies ; Female ; Humans ; Infant ; Infant, Newborn ; Infant, Premature - immunology ; Infectious Disease and Host Defense ; Lymphocyte Activation - immunology ; Male ; Membrane Glycoproteins - genetics ; Membrane Glycoproteins - metabolism ; Neonatal Sepsis - immunology ; Receptors, Antigen, T-Cell, gamma-delta - immunology ; Receptors, Antigen, T-Cell, gamma-delta - metabolism ; T-Lymphocyte Subsets - immunology ; T-Lymphocyte Subsets - metabolism</subject><ispartof>The Journal of experimental medicine, 2024-07, Vol.221 (7)</ispartof><rights>2024 Leon-Lara et al.</rights><rights>2024 Leon-Lara et al. 2024 Leon-Lara et al.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c385t-f79a6898915b8f7c3c323805405f3f75e2621d72448f82cfea55694bbb5d4c5e3</citedby><cites>FETCH-LOGICAL-c385t-f79a6898915b8f7c3c323805405f3f75e2621d72448f82cfea55694bbb5d4c5e3</cites><orcidid>0000-0001-6190-7923 ; 0009-0003-5471-7488 ; 0000-0001-5554-1937 ; 0000-0002-3624-6251 ; 0000-0002-9390-5348 ; 0000-0003-4336-7657 ; 0000-0002-8087-9419 ; 0000-0002-7188-5227 ; 0000-0002-9009-3559 ; 0000-0002-3265-6341 ; 0000-0003-4772-9352 ; 0000-0002-3261-9794 ; 0000-0002-5735-4526 ; 0000-0002-1212-8189 ; 0000-0002-8190-273X ; 0009-0008-7124-4359 ; 0009-0005-2670-2056 ; 0000-0002-8821-5895</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>230,314,780,784,885,27922,27923</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/38753245$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>León-Lara, Ximena</creatorcontrib><creatorcontrib>Fichtner, Alina S</creatorcontrib><creatorcontrib>Willers, Maike</creatorcontrib><creatorcontrib>Yang, Tao</creatorcontrib><creatorcontrib>Schaper, Katharina</creatorcontrib><creatorcontrib>Riemann, Lennart</creatorcontrib><creatorcontrib>Schöning, Jennifer</creatorcontrib><creatorcontrib>Harms, Anna</creatorcontrib><creatorcontrib>Almeida, Vicente</creatorcontrib><creatorcontrib>Schimrock, Anja</creatorcontrib><creatorcontrib>Janssen, Anika</creatorcontrib><creatorcontrib>Ospina-Quintero, Laura</creatorcontrib><creatorcontrib>von Kaisenberg, Constantin</creatorcontrib><creatorcontrib>Förster, Reinhold</creatorcontrib><creatorcontrib>Eberl, Matthias</creatorcontrib><creatorcontrib>Richter, Manuela F</creatorcontrib><creatorcontrib>Pirr, Sabine</creatorcontrib><creatorcontrib>Viemann, Dorothee</creatorcontrib><creatorcontrib>Ravens, Sarina</creatorcontrib><title>γδ T cell profiling in a cohort of preterm infants reveals elevated frequencies of CD83+ γδ T cells in sepsis</title><title>The Journal of experimental medicine</title><addtitle>J Exp Med</addtitle><description>Preterm infants are at high risk of developing neonatal sepsis. γδ T cells are thought to be an important set of effector cells in neonates. Here, γδ T cells were investigated in a longitudinal cohort of preterm neonates using next-generation sequencing, flow cytometry, and functional assays. During the first year of life, the Vγ9Vδ2 T cell subset showed dynamic phenotypic changes and elevated levels of fetal-derived Vγ9Vδ2 T cells were evident in infants with sepsis. Single-cell transcriptomics identified HLA-DRhiCD83+ γδ T cells in neonatal sepsis, which expressed genes related to antigen presentation. In vitro assays showed that CD83 was expressed on activated Vγ9Vδ2 T cells in preterm and term neonates, but not in adults. In contrast, activation of adult Vγ9Vδ2 T cells enhanced CD86 expression, which was presumably the key receptor to induce CD4 T cell proliferation. Together, we provide a map of the maturation of γδ T cells after preterm birth and highlight their phenotypic diversity in infections.</description><subject>Adult</subject><subject>Antigens, CD - genetics</subject><subject>Antigens, CD - metabolism</subject><subject>CD83 Antigen</subject><subject>Cohort Studies</subject><subject>Female</subject><subject>Humans</subject><subject>Infant</subject><subject>Infant, Newborn</subject><subject>Infant, Premature - immunology</subject><subject>Infectious Disease and Host Defense</subject><subject>Lymphocyte Activation - immunology</subject><subject>Male</subject><subject>Membrane Glycoproteins - genetics</subject><subject>Membrane Glycoproteins - metabolism</subject><subject>Neonatal Sepsis - immunology</subject><subject>Receptors, Antigen, T-Cell, gamma-delta - immunology</subject><subject>Receptors, Antigen, T-Cell, gamma-delta - metabolism</subject><subject>T-Lymphocyte Subsets - immunology</subject><subject>T-Lymphocyte Subsets - metabolism</subject><issn>0022-1007</issn><issn>1540-9538</issn><issn>1540-9538</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2024</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpVkctKAzEUhoMoWqs715KloKO5zmRWIvUKBTe6Dpn0RCMzk5pMCz6XPkefyRQv6CqQ8-U7-fkROqDklBIlzl6gO2WEcVqragONqBSkqCVXm2hECGMFJaTaQbspvRBChZDlNtrhqpKcCTlCr6v31Qd-wBbaFs9jcL71_RP2PTbYhucQBxxcHsAAscvXzvRDwhGWYNqEoYWlGWCGXYTXBfTWQ1rzk0vFj_EfdVobE8yTT3toy-W3sP99jtHj9dXD5LaY3t_cTS6mheVKDoWralOqWtVUNspVllvOuCI5nXTcVRJYyeisYkIop5h1YKQsa9E0jZwJK4GP0fmXd75oOphZ6IdoWj2PvjPxTQfj9f9J75_1U1hqSkley-tsOPo2xJDTpUF3Pq3TmB7CImlOpFQ1K0mZ0ZMv1MaQUgT3u4cSva5J55r0T00ZP_z7t1_4pxf-CbHmkUQ</recordid><startdate>20240701</startdate><enddate>20240701</enddate><creator>León-Lara, Ximena</creator><creator>Fichtner, Alina S</creator><creator>Willers, Maike</creator><creator>Yang, Tao</creator><creator>Schaper, Katharina</creator><creator>Riemann, Lennart</creator><creator>Schöning, Jennifer</creator><creator>Harms, Anna</creator><creator>Almeida, Vicente</creator><creator>Schimrock, Anja</creator><creator>Janssen, Anika</creator><creator>Ospina-Quintero, Laura</creator><creator>von Kaisenberg, Constantin</creator><creator>Förster, Reinhold</creator><creator>Eberl, Matthias</creator><creator>Richter, Manuela F</creator><creator>Pirr, Sabine</creator><creator>Viemann, Dorothee</creator><creator>Ravens, Sarina</creator><general>Rockefeller University Press</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope><scope>5PM</scope><orcidid>https://orcid.org/0000-0001-6190-7923</orcidid><orcidid>https://orcid.org/0009-0003-5471-7488</orcidid><orcidid>https://orcid.org/0000-0001-5554-1937</orcidid><orcidid>https://orcid.org/0000-0002-3624-6251</orcidid><orcidid>https://orcid.org/0000-0002-9390-5348</orcidid><orcidid>https://orcid.org/0000-0003-4336-7657</orcidid><orcidid>https://orcid.org/0000-0002-8087-9419</orcidid><orcidid>https://orcid.org/0000-0002-7188-5227</orcidid><orcidid>https://orcid.org/0000-0002-9009-3559</orcidid><orcidid>https://orcid.org/0000-0002-3265-6341</orcidid><orcidid>https://orcid.org/0000-0003-4772-9352</orcidid><orcidid>https://orcid.org/0000-0002-3261-9794</orcidid><orcidid>https://orcid.org/0000-0002-5735-4526</orcidid><orcidid>https://orcid.org/0000-0002-1212-8189</orcidid><orcidid>https://orcid.org/0000-0002-8190-273X</orcidid><orcidid>https://orcid.org/0009-0008-7124-4359</orcidid><orcidid>https://orcid.org/0009-0005-2670-2056</orcidid><orcidid>https://orcid.org/0000-0002-8821-5895</orcidid></search><sort><creationdate>20240701</creationdate><title>γδ T cell profiling in a cohort of preterm infants reveals elevated frequencies of CD83+ γδ T cells in sepsis</title><author>León-Lara, Ximena ; 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Here, γδ T cells were investigated in a longitudinal cohort of preterm neonates using next-generation sequencing, flow cytometry, and functional assays. During the first year of life, the Vγ9Vδ2 T cell subset showed dynamic phenotypic changes and elevated levels of fetal-derived Vγ9Vδ2 T cells were evident in infants with sepsis. Single-cell transcriptomics identified HLA-DRhiCD83+ γδ T cells in neonatal sepsis, which expressed genes related to antigen presentation. In vitro assays showed that CD83 was expressed on activated Vγ9Vδ2 T cells in preterm and term neonates, but not in adults. In contrast, activation of adult Vγ9Vδ2 T cells enhanced CD86 expression, which was presumably the key receptor to induce CD4 T cell proliferation. 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| subjects | Adult Antigens, CD - genetics Antigens, CD - metabolism CD83 Antigen Cohort Studies Female Humans Infant Infant, Newborn Infant, Premature - immunology Infectious Disease and Host Defense Lymphocyte Activation - immunology Male Membrane Glycoproteins - genetics Membrane Glycoproteins - metabolism Neonatal Sepsis - immunology Receptors, Antigen, T-Cell, gamma-delta - immunology Receptors, Antigen, T-Cell, gamma-delta - metabolism T-Lymphocyte Subsets - immunology T-Lymphocyte Subsets - metabolism |
| title | γδ T cell profiling in a cohort of preterm infants reveals elevated frequencies of CD83+ γδ T cells in sepsis |
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