A Tessellated Lymphoid Network Provides Whole-Body Antigen Surveillance in Zebrafish

ABSTRACT: T cells survey the host for cognate antigen in mammals by trafficking to and searching within lymph nodes distributed throughout the body. Non-mammalian jawed vertebrates lack lymph nodes but still maintain highly diverse repertoires of T cells. How these T cells find antigen in hosts devoid of lymph nodes remains wholly unclear. In this study, we exploit the in vivo imaging amenability of the zebrafish to investigate T cell organization, trafficking, and antigen surveillance in an animal completely lacking lymph nodes. We find that T cells organize into a previously undescribed whole-body scale-associated pattern that we have named the tessellated lymphoid network (TLN). We find that the TLN harbors significantly more T cells than the gills, gut, kidney, and spleen, as well as populations of antigen-presenting cells, suggesting a central role in adaptive immune responses in fish. Within the TLN, T cells perform a highly directional ballistic streaming mode of motility, allowing them to traffic through the host in a coordinated ventral-to-dorsal loop. Local infection results in a dramatic shift in T cell motility, from rapid streaming to a slower random walk in regions proximal to the infection. Here, T cells sequentially interact with and ultimately form stable contacts with antigen-presenting cells. Finally, T cells within the TLN of infected fish show transcriptional changes consistent with TCR signaling and subsequent T cell activation. The TLN thus provides a mechanism for T cells to both traffic through the host and, in the context of an infection, effectively scan for and detect antigen, mirroring the function of lymph nodes in mammals.

ORGANISM(S): Danio rerio

PROVIDER: GSE215189 | GEO | 2023/04/06

REPOSITORIES: GEO