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 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.