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

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. This response is critical for the acquisition of antiviral CD8+ T cell effector function, and its 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.

ORGANISM(S): Mus musculus

PROVIDER: GSE171690 | GEO | 2023/02/27

REPOSITORIES: GEO

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CD4+ T cells select unique P65, IRF1 and FOS dependen responses in APC for integration into antiviral CD8+ T cell immunity

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