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

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 naïve-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 naïve 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. Significance Statement In mammals, lymph nodes play a critical role in the initiation of adaptive immune responses by providing a dedicated place for T cells to scan antigen-presenting cells. Birds, reptiles, amphibians, and fish all maintain diverse repertoires of T cells but lack lymph nodes, raising questions about how adaptive immunity functions in lower jawed vertebrates. Here, we describe a novel network of lymphocytes in zebrafish that supports whole-body T cell trafficking and provides a site for antigen search, mirroring the function of mammalian lymph nodes. Within this network, T cells can prioritize large-scale trafficking or antigen scanning by toggling between two distinct modes of migration. This network provides valuable insights into the evolution of adaptive immunity. ### Competing Interest Statement The authors have declared no competing interest.