IFN-γ action in the media of the great elastic arteries, a novel immunoprivileged site
Albert J. Dal Canto, Paul E. Swanson, Andrew K. O’Guin, Samuel H. Speck, Herbert W. Virgin
Albert J. Dal Canto, Paul E. Swanson, Andrew K. O’Guin, Samuel H. Speck, Herbert W. Virgin
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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 inhibits γHV68 infection of primary aortic cells. IFN-γ–treated an...
IFN-γ inhibits γHV68 infection of primary aortic cells. IFN-γ–treated and untreated intimal/adventitial and medial cultures were evaluated 3 days after infection. In c and d nuclei were stained blue, muscle actin was stained red, and viral antigen was stained green. Uninfected cultures and infected cultures stained with control Ab’s demonstrated no viral antigen staining. (a and b) Phase-contrast microscopy of infected intimal/adventitial cultures with or without IFN-γ. (c) Representative field of infected medial cultures without IFN-γ treatment. (d) Representative field of infected medial cultures treated with IFN-γ. (e) EM of a cell with nuclear capsids from an infected, untreated medial culture. (f) EM of a cell without nuclear capsids from an infected, IFN-γ–treated medial culture. (g) Multiple fields were evaluated by dual immunofluorescence for viral antigen and muscle actin (three experiments) or by electron microscopy (two experiments). IF, immunofluorescence. The numbers above the bars represent the number of cells counted. For comparing results with or without IFN-γ treatment by IF, AP < 0.005, BP < 0.0002. For comparing results with or without IFN-γ by EM, AP = 0.0024, BP = 0.0013.