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

Nature immunology

Authors: Elise Gressier, Jonas Schulte-Schrepping, Lev Petrov, Sophia Brumhard, Paula Stubbemann, Anna Hiller, Benedikt Obermayer, Jasper Spitzer, Tomislav Kostevc, Paul G Whitney, Annabell Bachem, Alexandru Odainic, Carolien van de Sandt, Thi H O Nguyen, Thomas Ashhurst, Kayla Wilson, Clare V L Oates, Linden J Gearing, Tina Meischel, Katharina Hochheiser, Marie Greyer, Michele Clarke, Maike Kreutzenbeck, Sarah S Gabriel, Wolfgang Kastenmüller, Christian Kurts, Sarah L Londrigan, Axel Kallies, Katherine Kedzierska, Paul J Hertzog, Eicke Latz, Yu-Chen E Chen, Kristen J Radford, Michael Chopin, Jan Schroeder, Florian Kurth, Thomas Gebhardt, Leif E Sander, Birgit Sawitzki, Joachim L Schultze, Susanne V Schmidt, Sammy Bedoui

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.

© 2023. The Author(s), under exclusive licence to Springer Nature America, Inc.

PMID: 37188942

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