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bioRxiv · 10.1101/2021.09.26.461821

Transient dendritic cell activation diversifies the T cell response to acute infection

Hiam-Galvez, K. J.·Debarge, R.·Lareau, C. A.·Cho, N. W.·Yee, J. L.·Okholm, T. L. H.·Spitzer, M. H.
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Abstract

The precise timing of T cell priming during infection remains unclear. Here, we mapped the cellular dynamics of all immune lineages during acute infection with Listeria monocytogenes (Lm). We identified highly transient DC activation 2 days post-infection that functions as a critical time window for priming effector T cells. Regulation of this transient state was mediated by DC extrinsic IFN{gamma} provided by lymphocytes. Furthermore, antigen-specific T cells that arrive late to the site of priming and miss peak DC activation acquire only memory T cell fates. This temporal regulation of fate is recapitulated by CD8+ DCs ex vivo, suggesting that shifts in activation state of a single antigen presenting cell population alter T cell fates. These results uncover a novel mechanism for temporal regulation of T cell differentiation during a dynamic immune response to acute infection. One-Sentence SummaryThe immune system generates a balanced protective response through rapidly shifting activation states and recruitment of new cells into an ongoing inflammatory landscape.

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Hiam-Galvez, K. J., Debarge, R., Lareau, C. A., Cho, N. W., Yee, J. L., Okholm, T. L. H., Spitzer, M. H.. 2021-09-27. Transient dendritic cell activation diversifies the T cell response to acute infection. https://doi.org/10.1101/2021.09.26.461821

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