Association of T-Zone Reticular Networks and Conduits with Ectopic Lymphoid Tissues in Mice and Humans

Ectopic or tertiary lymphoid tissues (TLTs) are often induced at sites of chronic inflammation. They typically contain various hematopoietic cell types high endothelial venules and follicular dendritic cells; and are organized in lymph node like structures. Although fibroblastic stromal cells may play a role in TLT induction and persistence they have remained poorly defined. Herein we report that TLTs arising during inflammation in mice and humans in a variety of tissues (eg pancreas kidney liver and salivary gland) contain stromal cell networks consisting of podoplanin(+) T zone fibroblastic reticular cells (TRCs) distinct from follicular dendritic cells. Similar to lymph nodes TRCs were present throughout T cell rich areas and had dendritic cells associated with them. They expressed lymphotoxin (LT) ß receptor (LTßR) produced CCL21 and formed a functional conduit system. In rat insulin promoter CXCL13 transgenic pancreas the maintenance of TRC networks and conduits was partially dependent on LTßR and on lymphoid tissue inducer cells expressing LTßR ligands. In conclusion TRCs and conduits are hallmarks of secondary lymphoid organs and of well developed TLTs in both mice and humans and are likely to act as important scaffold and organizer cells of the T cell rich zone.