An In‐Vitro Model of T Cell Exit from the T Cell Zone Mediated by Sub‐Regional Co‐Existing CCL19 and CCL21 Fields in Lymph Nodes

Chemokines CCL19, CCL21 and their receptor CCR7 are known key mediators for T lymphocyte recruitment to lymph nodes (LNs) and navigation within LNs. The current model of T cell exit from LNs requires additional guiding signals. However, a critical mechanism is missing to facilitate T cell exit from the T cell zone (TCZ). Based on our previous experimental and modeling studies, we propose that LNs sub‐regional CCL19 and CCL21 fields mediate T cell exit from the TCZ through CCR7 signaling. In the present study, we analyzed CCL19 and CCL21 distribution profiles in different LNs sub‐regions of mouse LNs sections by immuno‐fluorescent staining and confocal microscopy, and our results conceptually support the hypothesized LNs sub‐regional CCL19 and CCL21 fields. Furthermore, we established an in‐vitro model to quantitatively examine the migration of activated human blood T cells in simulated LNs sub‐regional CCL19 and CCL21 fields followed by cell surface CCR7 expression analysis using a previously described microfluidic system. Our results suggest that CCL19 and CCL21 mediate T cells migration in LNs sub‐regions. In particular, the results suggest the sequential actions by specific co‐existing CCL19 and CCL21 fields in the TCZ periphery and in the region further beyond for mediating T cell exit from TCZ, which is correlated with altered surface CCR7 expression. This research was funded by NSERC, CFI and MHRC.