Gaps in access to emergency general surgery services exist across the United States, disproportionately affecting underserved, rural communities. Policy initiatives need to increase emergency general surgery capacity nationwide.

Highlights d Differences among naive CD4 + T cells are driven by TCR genes and chromatin modifiers d Pre-existing gene expression differences are maintained post-activation d CD5 hi naive CD4 + T cells have a greater propensity to become T FH cells d Distinct chromatin accessibility landscapes are established during thymic development

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SummaryCD4+ T cells have a remarkable potential to differentiate into diverse effector lineages following activation. Here, we probed the heterogeneity present among naïve CD4+ T cells before encountering their cognate antigen to ask whether their effector potential is modulated by pre-existing transcriptional and epigenetic differences. Using single-cell RNA sequencing, we showed that key drivers of variability are genes involved in T cell receptor (TCR) signaling. Using CD5 expression as a read-out of the strength of tonic TCR interactions with self-peptide MHC, and sorting on the ends of this self-reactivity spectrum, we find that pre-existing transcriptional differences among naïve CD4+ T cells impact follicular helper cell (TFH) versus non-TFH effector lineage choice. Moreover, our data implicate TCR signal strength during thymic development in establishing differences in naïve CD4 T cell chromatin landscapes that ultimately shape their effector potential.

Regulatory T cells (Tregs) continuously suppress autoreactive immune responses within tissues to prevent autoimmunity, yet the recirculatory behavior of Tregs between and within tissues enabling the maintenance of peripheral tolerance remains incompletely defined. Here, we quantified homing efficiency to and the dwell time of Tregs within secondary lymphoid organs (SLOs) and used intravital two‐photon microscopy to measure Treg surveillance behavior of dendritic cells. Tregs homed substantially less efficiently to SLOs compared with conventional CD4+ T cells (Tconvs), despite similar expression of homing receptors. Tregs remained on average 2–3 times longer within the LN than Tconvs before exiting, and retained Tregs differed from recirculating Tregs in phenotype, motility and interaction duration with dendritic cells. Taken together, these data revealed fundamental differences in Treg versus conventional T cell in vivo recirculation and migration behaviors, identified a Treg population with prolonged LN dwell time, and provided quantitative insight into their spatiotemporal behavior within LNs.