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| Item Type: | Article |
|---|---|
| Title: | CD4(+) T cell calibration of antigen-presenting cells optimizes antiviral CD8(+) T cell immunity |
| Creators: |
Gressier, E.  ORCID: https://orcid.org/0000-0003-0517-1610, Schulte-Schrepping, J. ORCID: https://orcid.org/0000-0001-7333-8924, Petrov, L., Brumhard, S., Stubbemann, P., Hiller, A., Obermayer, B. ORCID: https://orcid.org/0000-0002-9116-630X, Spitzer, J. ORCID: https://orcid.org/0000-0001-9696-2092, Kostevc, T., Whitney, P.G., Bachem, A., Odainic, A. ORCID: https://orcid.org/0000-0002-2806-6904, van de Sandt, C. ORCID: https://orcid.org/0000-0002-4155-7433, Nguyen, T.H.O. ORCID: https://orcid.org/0000-0002-9294-7693, Ashhurst, T. ORCID: https://orcid.org/0000-0001-7269-7773, Wilson, K. ORCID: https://orcid.org/0000-0003-2023-7964, Oates, C.V.L., Gearing, L.J. ORCID: https://orcid.org/0000-0003-3508-3056, Meischel, T. ORCID: https://orcid.org/0000-0002-0911-6574, Hochheiser, K., Greyer, M., Clarke, M., Kreutzenbeck, M., Gabriel, S.S. ORCID: https://orcid.org/0000-0002-6359-485X, Kastenmüller, W. ORCID: https://orcid.org/0000-0002-3835-1485, Kurts, C., Londrigan, S.L. ORCID: https://orcid.org/0000-0003-0989-4971, Kallies, A. ORCID: https://orcid.org/0000-0002-6312-6968, Kedzierska, K. ORCID: https://orcid.org/0000-0001-6141-335X, Hertzog, P.J., Latz, E. ORCID: https://orcid.org/0000-0003-1488-5666, Chen, Y.C.E., Radford, K.J. ORCID: https://orcid.org/0000-0001-6512-6323, Chopin, M., Schroeder, J., Kurth, Fl. ORCID: https://orcid.org/0000-0002-3807-473X, Gebhardt, T. ORCID: https://orcid.org/0000-0002-3768-9468, Sander, L.E. ORCID: https://orcid.org/0000-0002-0476-9947, Sawitzki, B., Schultze, J.L., Schmidt, S.V. and Bedoui, S. ORCID: https://orcid.org/0000-0002-7443-0543
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| 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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