GSE174629
Lymphatic migration of unconventional T cells promotes site-specific immunity in distinct lymph nodes
The adaptive limb of the immune system consists of antibody producing B cells and CD4 T helper and CD8 cytotoxic T cells. Besides these classical lymphocyte subsets, unconventional T cells exist that are characterized by a more limited repertoire of their TCR chains. Gamma delta (gd), mucosal-associated invariant (MAIT) and natural killer T cells (NKT) are the major cell types comprising this invariant T cell compartment. These cells are found throughout the body in the non- and lymphoid tissues and they recognize antigens that are linked to non-polymorphic antigen-presenting molecules like CD1 and MR1. Functionally, these cells typically recognize lipids, small-molecule metabolites and phosphoantigens that may be pathogen-derived or expressed by tissues in the context of activation or stress responses. Investigating these cell types on functional level as a group, we found that tissue-derived unconventional T cells constantly migrate like dendritic cells to draining lymph nodes. scRNAseq revealed transcriptional homogeneity of these subsets and shared functional outputs that as group, rather than separate entities, are critical to control bacterial infections. Importantly, since every tissue harbors a unique set of invariant T cells with specific differentiation states (Th1-like, Th2-like and Th17-like) every draining lymph node is as well populated by a unique composition of such cells. By comparing different lymph nodes using scRNA in an unbiased manner, we could resolve internodal differences and further demonstrate the functional consequences on humoral and cellular immune responses. The discovery that every lymph node mounts a unique immune response has a direct impact on vaccination strategies and immunotherapy approaches that aims at harnessing invariant T cells. Overall design: Skin draining lymph nodes from a CXCR6-GFP mouse were isolated and pooled. Single cell suspension was created and incubated with antibody mix for sorting. CXCR6-GFP high and CD44 positive cells were sorted and further processed for sequencing.