IFN-γ action in the media of the great elastic arteries, a novel immunoprivileged site
Albert J. Dal Canto, … , Samuel H. Speck, Herbert W. Virgin
Albert J. Dal Canto, … , Samuel H. Speck, Herbert W. Virgin
Published January 15, 2001
Citation Information: J Clin Invest. 2001;107(2):R15-R22. https://doi.org/10.1172/JCI11540.
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IFN-γ action in the media of the great elastic arteries, a novel immunoprivileged site

Abstract

Infection of medial smooth muscle cells with γ-herpesvirus 68 (γHV68) causes severe chronic vasculitis that is restricted to the great elastic arteries. We show here that persistence of disease in the great elastic arteries is (a) due to inefficient clearance of viral infection from this site 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 great elastic arteries. We found that IFN-γ acted on somatic cells during acute infection to prevent the establishment of medial infection and on hematopoietic cells to determine the severity of disease in this site. The immunoprivileged elastic media may provide a site for persistence of pathogens or self antigens leading to chronic vascular disease, a process regulated by IFN-γ actions on both somatic and hematopoietic cells. These concepts have significant implications for understanding immune responses contributing to or controlling chronic inflammatory diseases of the great vessels.

Authors

Albert J. Dal Canto, Paul E. Swanson, Andrew K. O’Guin, Samuel H. Speck, Herbert W. Virgin

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IFN-γ prevents chronic elastic arteritis by effects on somatic cells but...
IFN-γ prevents chronic elastic arteritis by effects on somatic cells but regulates the nature of the pathology by effects on hematopoietic cells. Reciprocal bone marrow reconstitutions were performed between IFN-γR–/– and 129Ev/Sv mice, and arteritis was evaluated for 12 weeks after γHV68 infection. Numbers above bars represent the number of mice within a group. Boxed numbers represent average lesion scores for a group. Data are pooled from four independent experiments. For incidence of disease, P = 0.0001 comparing group A with D, and P = 0.0004 comparing group B with C. For severity of disease, P < 0.0001 comparing groups A and B. NA, lesion scores not applicable.