IFN-gamma action in the media of the great elastic arteries, a novel immunoprivileged site

Infection of medial smooth muscle cells with gamma -herpesvirus 68 (gamma H V68) causes severe chronic vasculitis that is restricted to the great elast ic arteries. We show here that persistence of disease in the great elastic arteries is (a) due to inefficient clearance of viral infection from this s ite compared with other organs or other vascular sites, and (b) associated with failure of T cells and macrophages to enter the virus-infected elastic media. These findings demonstrate immunoprivilege of the media of the grea t elastic arteries. We found that IFN-gamma acted on somatic cells during a cute infection to prevent the establishment of medial infection and on hema topoietic cells to determine the severity of disease in this sire. The immu noprivileged elastic media may provide a site for persistence of pathogens or self antigens leading to chronic vascular disease, a process regulated b y IFN-gamma actions on both somatic and hematopoietic cells. These concepts have significant implications for understanding immune responses contribut ing to or controlling chronic inflammatory diseases of the great vessels.