A novel role for blood endothelial cells in the development and maintenance of immune memory (110.17)

Abstract Vaccination with recombinant human adenovirus serotype 5 (rHuAd5) drives a CD8+ T cell response that is dominated by effector and effector memory cells. In investigating the immunobiological mechanisms that result in this effector-skewed response, we previously showed that non-haematopoietic cells play a key role in defining the rHuAd5-elicited CD8+ T cell memory population. Furthermore, maintenance of this memory population relies upon sustained transgene expression from the adenovirus vector. While we know that following vaccination rHuAd5 drains to local lymph nodes, long-term antigen persistence occurs outside this location, since surgical removal of these nodes does not impact the nature of the memory response. Here, we show that following intramuscular vaccination, the adenovirus transgene is predominantly detected in the perinodal adipose tissue, in addition to draining lymph nodes and the muscle injection site itself. In all three locations, blood endothelial cells are the primary cell type that express the adenovirus-encoded antigen, strongly indicating that this radio-resistant cell population may have a role in presenting antigen to CD8+ T cells and ultimately in defining the memory response. Long-term antigen presentation from this cell compartment may represent a mechanism to sustain CD8+ T cell memory within the circulation and to ensure adequate protective immunity is maintained in multiple organs.