Antigen archiving and management by lymphatic endothelial cells. (INC1P.363)

Abstract

Abstract Antigen derived from virus infections such as influenza and Vesicular Stomatitis Virus (VSV) can persist well beyond the natural rise and fall of the adaptive immune response against the infection. Antigen can similarly persist following both viral Vaccinia challenge and subunit vaccination. Surprisingly, persisting antigen from either Vaccinia or subunit vaccination is captured and maintained by a stromal cell subset: Lymphatic Endothelial Cells (LECs). The duration of antigen persistence is directly correlated with antigen dose and pattern recognition receptor (PRR) activation. PRR induced inflammation leads to LEC proliferation followed by antigen persistence in the lymph node. The coupling of LEC proliferation and antigen capture identifies a novel mechanism by which the secondary lymphoid stroma stores, or “archives”, antigens for extended periods of time after antigen challenge. Consistent with the idea that viral antigen persistence impacts the function of circulating memory T cells, we find that vaccine elicited antigen archiving on LECs has a significant impact on the fate of circulating memory T cells. As such, antigen archiving on LECs leads to increased production of interferon gamma and interleukin 2 by antigen specific CD8 T cells and protection against secondary infection. These findings may broadly impact our understanding of how lymph node stroma, specifically LECs, are involved in i) managing antigen and ii) protecting against re-infection.