TY - JOUR
T1 - CD4+ T cell calibration of antigen-presenting cells optimizes antiviral CD8+ T cell immunity
AU - Gressier, Elise
AU - Schulte-Schrepping, Jonas
AU - Petrov, Lev
AU - Brumhard, Sophia
AU - Stubbemann, Paula
AU - Hiller, Anna
AU - Obermayer, Benedikt
AU - Spitzer, Jasper
AU - Kostevc, Tomislav
AU - Whitney, Paul G.
AU - Bachem, Annabell
AU - Odainic, Alexandru
AU - van de Sandt, Carolien
AU - Nguyen, Thi H.O.
AU - Ashhurst, Thomas
AU - Wilson, Kayla
AU - Oates, Clare V.L.
AU - Gearing, Linden J.
AU - Meischel, Tina
AU - Hochheiser, Katharina
AU - Greyer, Marie
AU - Clarke, Michele
AU - Kreutzenbeck, Maike
AU - Gabriel, Sarah S.
AU - Kastenmüller, Wolfgang
AU - Kurts, Christian
AU - Londrigan, Sarah L.
AU - Kallies, Axel
AU - Kedzierska, Katherine
AU - Hertzog, Paul J.
AU - Latz, Eicke
AU - Chen, Yu Chen E.
AU - Radford, Kristen J.
AU - Chopin, Michael
AU - Schroeder, Jan
AU - Kurth, Florian
AU - Gebhardt, Thomas
AU - Sander, Leif E.
AU - Sawitzki, Birgit
AU - Schultze, Joachim L.
AU - Schmidt, Susanne V.
AU - Bedoui, Sammy
N1 - Funding Information:
We thank L. Loyal, A. Thiel, C. Iwert, C. Meisel, R. Rudraraju and K. Subbarao for discussions, F. Koay and D. Godfrey for Cxcr6–/–mice and M. Cragg for the human CD40 antibody. The technical expertise in breeding, maintaining and manipulating specific pathogen-free mice by the Doherty Bioresources facility is gratefully acknowledged. We also thank D. Kunkel and J. Keye from the BIH Flow and Mass Cytometry Core Facility for sample acquisition. We are grateful to the Genomics platform at the Walter & Eliza Hall Institute for Medical Research in Melbourne. Our research is supported by the National Health and Medical Research Council of Australia (APP1124815, APP1071916, APP1103895 and APP1154540), the Sylvia & Charles Viertel Charitable Foundation, a 350th Anniversary Research Grant from Merck KgGA, The Advanced Genomic Collaboration and the International Research Training Group (IRTG2168) funded by the German Research Council and The University of Melbourne. B.S. received support from the European Union’s Horizon 2020 research and innovation program (INsTRuCT, 860003) and the German Federal Ministry of Education and Research (BMBF) project RECAST (01KI20337). A.H. is supported by the Jürgen Manchot Foundation. E.L. and S.V.S were supported by the German Federal Ministry of Education and Research through the COVIMMUN project (grant 01KI20343). Furthermore, E.L. received support by the Deutsche Forschungsgemeinschaft (DFG, German Research Foundation), grant 397484323, TRR259. We thank the NGS Core Facility of the University Hospital Bonn for library preparation and the generation of the sequencing data. We also would like to thank the German COVID-19 OMICS Initiative (DeCOI) for providing access to scRNA-seq data. J.L.S. was supported by the DFG (IRTG2168, INST 217/1011-1 and INST 217/1017-1, Excellence Cluster ImmunoSensation2(EXC2151/1) under project number 390873048) and SYSCID, receiving funding from the European Union’s Horizon 2020 research and innovation program under grant agreement number 733100. We are indebted to the participants, their families and the hospital staff for support, without whom this study would not have been possible.
Funding Information:
We thank L. Loyal, A. Thiel, C. Iwert, C. Meisel, R. Rudraraju and K. Subbarao for discussions, F. Koay and D. Godfrey for Cxcr6 mice and M. Cragg for the human CD40 antibody. The technical expertise in breeding, maintaining and manipulating specific pathogen-free mice by the Doherty Bioresources facility is gratefully acknowledged. We also thank D. Kunkel and J. Keye from the BIH Flow and Mass Cytometry Core Facility for sample acquisition. We are grateful to the Genomics platform at the Walter & Eliza Hall Institute for Medical Research in Melbourne. Our research is supported by the National Health and Medical Research Council of Australia (APP1124815, APP1071916, APP1103895 and APP1154540), the Sylvia & Charles Viertel Charitable Foundation, a 350th Anniversary Research Grant from Merck KgGA, The Advanced Genomic Collaboration and the International Research Training Group (IRTG2168) funded by the German Research Council and The University of Melbourne. B.S. received support from the European Union’s Horizon 2020 research and innovation program (INsTRuCT, 860003) and the German Federal Ministry of Education and Research (BMBF) project RECAST (01KI20337). A.H. is supported by the Jürgen Manchot Foundation. E.L. and S.V.S were supported by the German Federal Ministry of Education and Research through the COVIMMUN project (grant 01KI20343). Furthermore, E.L. received support by the Deutsche Forschungsgemeinschaft (DFG, German Research Foundation), grant 397484323, TRR259. We thank the NGS Core Facility of the University Hospital Bonn for library preparation and the generation of the sequencing data. We also would like to thank the German COVID-19 OMICS Initiative (DeCOI) for providing access to scRNA-seq data. J.L.S. was supported by the DFG (IRTG2168, INST 217/1011-1 and INST 217/1017-1, Excellence Cluster ImmunoSensation (EXC2151/1) under project number 390873048) and SYSCID, receiving funding from the European Union’s Horizon 2020 research and innovation program under grant agreement number 733100. We are indebted to the participants, their families and the hospital staff for support, without whom this study would not have been possible. –/–
Publisher Copyright:
© 2023, The Author(s), under exclusive licence to Springer Nature America, Inc.
PY - 2023/6
Y1 - 2023/6
N2 - Antiviral CD8+ T cell immunity depends on the integration of various contextual cues, but how antigen-presenting cells (APCs) consolidate these signals for decoding by T cells remains unclear. Here, we describe gradual interferon-α/interferon-β (IFNα/β)-induced transcriptional adaptations that endow APCs with the capacity to rapidly activate the transcriptional regulators p65, IRF1 and FOS after CD4+ T cell-mediated CD40 stimulation. While these responses operate through broadly used signaling components, they induce a unique set of co-stimulatory molecules and soluble mediators that cannot be elicited by IFNα/β or CD40 alone. These responses are critical for the acquisition of antiviral CD8+ T cell effector function, and their activity in APCs from individuals infected with severe acute respiratory syndrome coronavirus 2 correlates with milder disease. These observations uncover a sequential integration process whereby APCs rely on CD4+ T cells to select the innate circuits that guide antiviral CD8+ T cell responses.
AB - Antiviral CD8+ T cell immunity depends on the integration of various contextual cues, but how antigen-presenting cells (APCs) consolidate these signals for decoding by T cells remains unclear. Here, we describe gradual interferon-α/interferon-β (IFNα/β)-induced transcriptional adaptations that endow APCs with the capacity to rapidly activate the transcriptional regulators p65, IRF1 and FOS after CD4+ T cell-mediated CD40 stimulation. While these responses operate through broadly used signaling components, they induce a unique set of co-stimulatory molecules and soluble mediators that cannot be elicited by IFNα/β or CD40 alone. These responses are critical for the acquisition of antiviral CD8+ T cell effector function, and their activity in APCs from individuals infected with severe acute respiratory syndrome coronavirus 2 correlates with milder disease. These observations uncover a sequential integration process whereby APCs rely on CD4+ T cells to select the innate circuits that guide antiviral CD8+ T cell responses.
UR - http://www.scopus.com/inward/record.url?scp=85159275992&partnerID=8YFLogxK
U2 - 10.1038/s41590-023-01517-x
DO - 10.1038/s41590-023-01517-x
M3 - Article
C2 - 37188942
AN - SCOPUS:85159275992
SN - 1529-2908
VL - 24
SP - 979
EP - 990
JO - Nature Immunology
JF - Nature Immunology
IS - 6
ER -