Immune Recognition of Vascular Endothelial Cells

Immunologists think about central or peripheral tolerance, depending on whether the potential antigen is found within the lymphoid tissues. The central immune system includes the bloodstream, lymph, and primary lymphoid organs such as the thymus and lymph nodes. From an immunologist's perspective, the "periphery" is all the body's non-lymphoid organs and tissues. This distinction overlooks the interface between these tissues - the endothelium - the single cell layer that lines the blood and lymph vessels. Given the pervasiveness of blood vessels, it is not surprising that endothelial cells (EC) have been implicated in many immune processes, most notably atherosclerosis and transplant rejection. These investigators directly tested the ability of the immune system to recognize a new protein expressed by EC using two strains of transgenic mice that express beta-galactosidase only in their EC because their genomes have the beta-gal gene, lacZ , under control of promoters specific for endothelial cells. One transgenic line, VWF-lacZ, expresses beta-gal only in heart and brain endothelium. A second line, TIE2-lacZ, expresses beta-gal in practically all endothelial cells. Upon immunization with beta-gal protein, these mice responded normally, generating strong antibodies and T cell responses. They also responded normally after immunization with a DNA vector driving expression of beta-gal. After immunization, vascular EC in the transgenic mice continued to express beta-gal and the vessels showed no signs of inflammation when analyzed microscopically. This suggested the EC were simply ignored. However, TIE2-lacZ skin (which contains beta-gal+ EC) stimulated
beta-gal specific antibodies when it was transplanted onto non-transgenic littermates. Moreover, no antibodies were stimulated upon transplantation onto VWF-lacZ mice, suggesting that the immune system in these mice were tolerant, not ignorant, of the beta-gal expressed by EC. They conclude that the immune system subtly tolerates and does not ignore EC proteins.
Annette L Rothermel, Yinong Wang, Jeffrey Schechner, Barry Mook-Kanamori, William C Aird, Jordan S Pober, George Tellides and David R Johnson. Endothelial cells present antigens in vivo BMC Immunology March 2004, 5:5