CD4 T cell calibration of antigen-presenting cells optimizes antiviral CD8 T cell immunity

E Gressier; J Schulte-Schrepping; L Petrov; S Brumhard; P Stubbemann; A Hiller; B Obermayer; J Spitzer; T Kostevc; PG Whitney; A Bachem; A Odainic; C van de Sandt; THO Nguyen; T Ashhurst; K Wilson; CVL Oates; LJ Gearing; T Meischel; K Hochheiser; M Greyer; M Clarke; M Kreutzenbeck; SS Gabriel; W Kastenmüller; C Kurts; SL Londrigan; A Kallies; K Kedzierska; PJ Hertzog; E Latz; YCE Chen; KJ Radford; M Chopin; J Schroeder; F Kurth; T Gebhardt; LE Sander; B Sawitzki; JL Schultze; SV Schmidt; S Bedoui

Journal article

CD4 T cell calibration of antigen-presenting cells optimizes antiviral CD8 T cell immunity

E Gressier, J Schulte-Schrepping, L Petrov, S Brumhard, P Stubbemann, A Hiller, B Obermayer, J Spitzer, T Kostevc, PG Whitney, A Bachem, A Odainic, C van de Sandt, THO Nguyen, T Ashhurst, K Wilson, CVL Oates, LJ Gearing, T Meischel, K Hochheiser Show all

Nature Immunology | NATURE PORTFOLIO | Published : 2023

DOI: 10.1038/s41590-023-01517-x

Abstract

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..

View full abstract

University of Melbourne Researchers

Annabell Bachem Author

Carolien van de Sandt Author

Oanh Nguyen Author

Kayla Wilson Author

Related Projects (2)

LIMITING THE IMPACT OF INFLUENZA

The development of better ways to prevent and treat influenza infection will be a major step forward in lessening the impact of the virus in..

MICROBIOTA AND T CELL IMMUNITY

Our research has identified unprecedented communications between the microbes that colonize our body’s surfaces and killer T cell immunity. ..

Grants

Awarded by Sylvia and Charles Viertel Charitable Foundation

Funding Acknowledgements

We thank L. Loyal, A. Thiel, C. Iwert, C. Meisel, R. Rudraraju and K. Subbarao for discussions, F. Koay and D. Godfrey for Cxcr6<SUP>-/-</SUP> 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 Juergen 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.