澳大利亚墨尔本大学Sammy Bedoui、Elise Gressier研究团队取得一项新突破。他们的研究表明抗原呈递细胞（APC）对CD4⁺ T细胞的校准可增强CD8⁺ T细胞抗病毒免疫。2023年5月15日，国际学术期刊《自然-免疫学》发表了这一成果。

研究人员发现了由干扰素-α/干扰素-β（IFNα/β）诱导的转录适应，在CD4⁺ T细胞介导的CD40刺激后赋予APC快速激活转录调节因子p65、IRF1和FOS的能力。虽然这些反应通过广泛使用的信号组分起作用，但它们诱导一组独特的共刺激分子和可溶性介质，这些分子和可溶性介质不能单独由IFNα/β或CD40产生。这些反应对于获得抗病毒CD8⁺ T细胞效应功能至关重要，并且与感染严重急性呼吸综合征冠状病毒2个体APC的活性与较轻的疾病相关。这些观察结果揭示了一个顺序整合的先天调控回路，其中APC依靠CD4⁺ T细胞来选择指导抗病毒CD8⁺ T细胞反应。

据悉，CD8⁺ T细胞抗病毒免疫取决于环境因素的整合，但仍不清楚APC如何稳定这些信号以供T细胞激活。

附：英文原文

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

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., Kastenmller, 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

Issue&Volume: 2023-05-15

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.

DOI: 10.1038/s41590-023-01517-x

Source: https://www.nature.com/articles/s41590-023-01517-x