Go to JCI Insight
  • About
  • Editors
  • Consulting Editors
  • For authors
  • Publication ethics
  • Publication alerts by email
  • Advertising
  • Job board
  • Contact
  • Clinical Research and Public Health
  • Current issue
  • Past issues
  • By specialty
    • COVID-19
    • Cardiology
    • Gastroenterology
    • Immunology
    • Metabolism
    • Nephrology
    • Neuroscience
    • Oncology
    • Pulmonology
    • Vascular biology
    • All ...
  • Videos
    • Conversations with Giants in Medicine
    • Video Abstracts
  • Reviews
    • View all reviews ...
    • Complement Biology and Therapeutics (May 2025)
    • Evolving insights into MASLD and MASH pathogenesis and treatment (Apr 2025)
    • Microbiome in Health and Disease (Feb 2025)
    • Substance Use Disorders (Oct 2024)
    • Clonal Hematopoiesis (Oct 2024)
    • Sex Differences in Medicine (Sep 2024)
    • Vascular Malformations (Apr 2024)
    • View all review series ...
  • Viewpoint
  • Collections
    • In-Press Preview
    • Clinical Research and Public Health
    • Research Letters
    • Letters to the Editor
    • Editorials
    • Commentaries
    • Editor's notes
    • Reviews
    • Viewpoints
    • 100th anniversary
    • Top read articles

  • Current issue
  • Past issues
  • Specialties
  • Reviews
  • Review series
  • Conversations with Giants in Medicine
  • Video Abstracts
  • In-Press Preview
  • Clinical Research and Public Health
  • Research Letters
  • Letters to the Editor
  • Editorials
  • Commentaries
  • Editor's notes
  • Reviews
  • Viewpoints
  • 100th anniversary
  • Top read articles
  • About
  • Editors
  • Consulting Editors
  • For authors
  • Publication ethics
  • Publication alerts by email
  • Advertising
  • Job board
  • Contact
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.
View: Text | PDF
Rapid Publication

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

  • Text
  • PDF
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

×

Figure 4

Options: View larger image (or click on image) Download as PowerPoint
Incidence and severity of chronic elastic arteritis in wild-type mice in...
Incidence and severity of chronic elastic arteritis in wild-type mice infected with high doses of γHV68 with or without transient depletion of IFN-γ. Mice were infected with the indicated doses of γHV68 with or without depletion of IFN-γ and evaluated for arteritis on H&E-stained sections 5.5 to 10 weeks after infection. (a) The incidence of arteritis in various groups is presented. Seven of 19 mice infected with 17 to 20 × 107 PFU γHV68 died within 7 days. Twelve of 14 mice infected with 34 to 50 × 107 PFU died within 7 days. Data for transient depletions are from two independent experiments. Data for no depletions are from 4–5 independent experiments. AP = 0.0062; BP = 0.0043. (b) Lesion at the aortic base of a 129Ev/Sv mouse sacrificed 10 weeks after infection with 108 PFU γHV68. Lesions in transiently IFN-γ–depleted 129Ev/Sv mice have similar histology (lesion scores for 25 mice from both groups combined = 2.0 ± 0.2; P < 0.0001 for scores compared with IFN-γR–/– mice, P = 0.001 compared with chronically depleted wild-type mice). (c) High-power view of boxed region in b. (d) Lesion at the aortic base of a chronically IFN-γ–depleted 129Ev/Sv mouse sacrificed 6 weeks after infection with 5 × 107 PFU γHV68 (lesion scores for four mice = 4.0 ± 0.7). Arteritis in IFN-γR–/– mice has similar histology (lesion scores for 16 mice = 5.0 ± 0). (e) High-power view of boxed region in d. The black lines show the boundaries of the media. Adv, adventitia; M, media; I, intima; L, lumen; V, aortic valve. ND, not determined.

Copyright © 2025 American Society for Clinical Investigation
ISSN: 0021-9738 (print), 1558-8238 (online)

Sign up for email alerts