학술논문
CD4+ T cell calibration of antigen-presenting cells optimizes antiviral CD8+ T cell immunity
Document Type
Original Paper
Author
Gressier, Elise; Schulte-Schrepping, Jonas; Petrov, Lev; Brumhard, Sophia; Stubbemann, Paula; Hiller, Anna; Obermayer, Benedikt; Spitzer, Jasper; Kostevc, Tomislav; Whitney, Paul G.; Bachem, Annabell; Odainic, Alexandru; van de Sandt, Carolien; Nguyen, Thi H. O.; Ashhurst, Thomas; Wilson, Kayla; Oates, Clare V. L.; Gearing, Linden. J.; Meischel, Tina; Hochheiser, Katharina; Greyer, Marie; Clarke, Michele; Kreutzenbeck, Maike; Gabriel, Sarah S.; Kastenmüller, Wolfgang; Kurts, Christian; Londrigan, Sarah L.; Kallies, Axel; Kedzierska, Katherine; Hertzog, Paul J.; Latz, Eicke; Chen, Yu-Chen E.; Radford, Kristen J.; Chopin, Michael; Schroeder, Jan; Kurth, Florian; Gebhardt, Thomas; Sander, Leif E.; Sawitzki, Birgit; Schultze, Joachim L.; Schmidt, Susanne V.; Bedoui, Sammy
Source
Nature Immunology. 24(6):979-990
Subject
Language
English
ISSN
1529-2908
1529-2916
1529-2916
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+ 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.
Bedoui and colleagues describe a sequential process of integration of innate and CD40-delivered signals in APCs, which optimizes their capacity to drive antiviral CD8+ T cell responses.
Bedoui and colleagues describe a sequential process of integration of innate and CD40-delivered signals in APCs, which optimizes their capacity to drive antiviral CD8