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

Gressier, E.; Schulte-Schrepping, J.; Petrov, L.; Brumhard, S.; Stubbemann, P.; Hiller, A.; Obermayer, B.; Spitzer, J.; Kostevc, T.; Whitney, P.G.; Bachem, A.; Odainic, A.; van de Sandt, C.; Nguyen, T.H.O.; Ashhurst, T.; Wilson, K.; Oates, C.V.L.; Gearing, L.J.; Meischel, T.; Hochheiser, K.; Greyer, M.; Clarke, M.; Kreutzenbeck, M.; Gabriel, S.S.; Kastenmüller, W.; Kurts, C.; Londrigan, S.L.; Kallies, A.; Kedzierska, K.; Hertzog, P.J.; Latz, E.; Chen, Y.C.E.; Radford, K.J.; Chopin, M.; Schroeder, J.; Kurth, Fl.; Gebhardt, T.; Sander, L.E.; Sawitzki, B.; Schultze, J.L.; Schmidt, S.V.; Bedoui, S.

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

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Item Type:	Article
Title:	CD4(+) T cell calibration of antigen-presenting cells optimizes antiviral CD8(+) T cell immunity
Creators Name:	Gressier, E., Schulte-Schrepping, J., Petrov, L., Brumhard, S., Stubbemann, P., Hiller, A., Obermayer, B., Spitzer, J., Kostevc, T., Whitney, P.G., Bachem, A., Odainic, A., van de Sandt, C., Nguyen, T.H.O., Ashhurst, T., Wilson, K., Oates, C.V.L., Gearing, L.J., Meischel, T., Hochheiser, K., Greyer, M., Clarke, M., Kreutzenbeck, M., Gabriel, S.S., Kastenmüller, W., Kurts, C., Londrigan, S.L., Kallies, A., Kedzierska, K., Hertzog, P.J., Latz, E., Chen, Y.C.E., Radford, K.J., Chopin, M., Schroeder, J., Kurth, Fl., Gebhardt, T., Sander, L.E., Sawitzki, B., Schultze, J.L., Schmidt, S.V. and Bedoui, S.
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.
Keywords:	Antigen-Presenting Cells, Antiviral Agents, CD4-Positive T-Lymphocytes, CD40 Antigens, CD8-Positive T-Lymphocytes, COVID-19, Calibration, Interferon-Alpha
Source:	Nature Immunology
ISSN:	1529-2908
Publisher:	Nature Publishing Group
Volume:	24
Number:	6
Page Range:	979-990
Number of Pages:	12
Date:	June 2023
Official Publication:	https://doi.org/10.1038/s41590-023-01517-x
PubMed:	View item in PubMed

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