AUTHOR=Curato Caterina , Bernshtein Biana , Zupancič Eva , Dufner Almut , Jaitin Diego , Giladi Amir , David Eyal , Chappell-Maor Louise , Leshkowitz Dena , Knobeloch Klaus-Peter , Amit Ido , Florindo Helena F. , Jung Steffen 

TITLE=DC Respond to Cognate T Cell Interaction in the Antigen-Challenged Lymph Node

JOURNAL=Frontiers in Immunology

VOLUME=10

YEAR=2019

URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2019.00863

DOI=10.3389/fimmu.2019.00863

ISSN=1664-3224

ABSTRACT=<p>Dendritic cells (DC) are unrivaled in their potential to prime naive T cells by presenting antigen and providing costimulation. DC are furthermore believed to decode antigen context by virtue of pattern recognition receptors and to polarize T cells through cytokine secretion toward distinct effector functions. Diverse polarized T helper (T<sub>H</sub>) cells have been explored in great detail. In contrast, studies of instructing DC have to date largely been restricted to <italic>in vitro</italic> settings or adoptively transferred DC. Here we report efforts to unravel the DC response to cognate T cell encounter in antigen-challenged lymph nodes (LN). Mice engrafted with antigen-specific T cells were immunized with nanoparticles (NP) entrapping adjuvants and absorbed with antigen to study the immediate DC response to T cell encounter using bulk and single cell RNA-seq profiling. NP induced robust antigen-specific T<sub>H</sub>1 cell responses with minimal bystander activation. Fluorescent-labeled NP allowed identification of antigen-carrying DC and focus on transcriptional changes in DC that encounter T cells. Our results support the existence of a bi-directional crosstalk between DC and T cells that promotes T<sub>H</sub>1 responses, including involvement of the ubiquitin-like molecule Isg15 that merits further study.</p>