A tessellated lymphoid network provides whole-body T cell surveillance in zebrafish

Abstract

Homeostatic trafficking to lymph nodes allows T cells to efficiently survey the host for cognate antigen. Non-mammalian jawed vertebrates lack lymph nodes but maintain similarly diverse T cell pools. Here, we exploit in vivo imaging of transparent zebrafish to investigate how T cells organize and survey for antigen in an animal devoid of lymph nodes. We find that naive-like T cells in zebrafish organize into a previously undescribed whole-body lymphoid network that supports streaming migration and coordinated trafficking through the host. This network has the cellular hallmarks of a mammalian lymph node, including naive T cells and CCR7-ligand expressing non-hematopoietic cells, and facilitates rapid collective migration. During infection, T cells transition to a random walk that supports antigen presenting cell interactions and subsequent activation. Our results reveal that T cells can toggle between collective migration and individual random walks to prioritize either large-scale trafficking or antigen search in situ. This novel lymphoid network thus facilitates whole-body T cell trafficking and antigen surveillance in the absence of a lymph node system.

Identification of a pharyngeal mucosal lymphoid organ in zebrafish and other teleosts: Tonsils in fish?

“…S4 (A to D). In addition, the existence of NELO could be confirmed based on the expression of the kinase lck gene using the Tg(lck:EGFP) transgenic adult zebrafish ( 18 , 42 ), in which enhanced green fluorescent protein (EGFP) is highly expressed in T lymphocytes (fig. S4, E and F).…”

“…Further analysis showed that this lymphoid network extended beyond the branchial cavity region (fig. S11), likely connecting with the tessellated lymphoid network ( 42 ) via the operculum opening, as well as linking the pharyngeal epithelium and the esophagus epithelium (fig. S11A).…”

CCR7 acts as both a sensor and a sink for CCL19 to coordinate collective leukocyte migration

“…Moreover, immune cell density is extremely high in lymph nodes, leaving ample opportunity for local regulation of CCL19 concentration by CCR7-mediated scavenging ( 21 ). Recently, it was found that in zebrafish, a lower-jawed organism without well-organized lymph nodes, T cells migrated collectively in a CCR7-dependent manner in the special tessellated lymphoid network to facilitate whole-body surveillance ( 50 ). Although in our experiment, T cells were not able to migrate efficiently by themselves in a uniform CCL19 field, it is possible that self-generated chemokine gradients could contribute to collective T cell migration in such settings.…”

Single-cell transcriptional landscape of temporal neutrophil response to burn wound in larval zebrafish

“…Single-cell transcriptome data from adult zebrafish tessellated lymphoid network was processed as previously described (18). Neutrophil was annotated based on the top differentially expressed genes identified by Wilcoxon rank-sum test ( FindAllMarkers with log2 fold change threshold of 0.25 and positive only) and subsetted for sub-clustering.…”