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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

Project description:Antiviral CD8+ T cell immunity depends on the integration of varying contextual cues, but how antigen presenting cells (APC ) consolidate these signals for decoding by T cells remains unclear. We describe gradual IFN-α/β-induced transcriptional adaptations that endowed APC with the capacity to rapidly activate the transcriptional regulators P65, IRF1 and FOS upon CD4+ T cell-mediated CD40 stimulation. While these responses operated through broadly utilized signaling components, they induced a unique set of costimulatory molecules and soluble mediators that could not be elicited by IFN-α/β or CD40 alone. This response was critical for the acquisition of antiviral CD8+ T cell effector function, and its activity in APC from patients infected with severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) correlated with milder disease. These observations uncover a sequential integration process whereby APC rely on CD4+ T cells to select the innate circuits that guide antiviral CD8+ T cell responses.

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